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Yang H, Zhou Y, Ying B, Dong X, Qian Q, Gao S. Effects of human umbilical cord mesenchymal stem cell-derived exosomes in the rat osteoarthritis models. Stem Cells Transl Med 2024; 13:803-811. [PMID: 38913985 PMCID: PMC11328936 DOI: 10.1093/stcltm/szae031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 02/16/2024] [Indexed: 06/26/2024] Open
Abstract
Mesenchymal stem cells (MSCs) offer great potential for treatment of osteoarthritis (OA) by promoting articular cartilage regeneration via paracrine secretion of exosomes; however, the underlying mechanisms are not fully understood. This study aimed to explore the therapeutic effects of exosomes secreted by human umbilical cord-derived MSCs (hUC-MSCs) in rat models of OA and reveal the underlying mechanisms. UC-MSCs and UC-MSC-exosomes were prepared and identified by transmission electron microscopy and flow cytometry. IL-1β-induced OA chondrocytes and the operation and collagenase-induced OA rat models were established. The results of micro-computed tomography, histology, and immunohistochemistry showed that UC-MSC-exosomes promoted cartilage regeneration in OA rats. ELISA results showed that the levels of synovial fluid cytokines, TNF-α, IL-1β, and IL-6, were lower in exosome therapy group than control group in both OA rat models. Exosome treatment significantly downregulated the expression of MMP-13 and ADAMTS-5 in chondrocytes stimulated by IL-1β, and upregulated collagen II expression. These findings suggest that hUC-MSC-exosomes offer a promising option for the therapy for OA.
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Affiliation(s)
- Huanfeng Yang
- Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200120, People's Republic of China
- Department of R&D, Oricell Therapeutics, Shanghai, 201203, People's Republic of China
| | - Yiqin Zhou
- Department of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, People's Republic of China
| | - Bi Ying
- Department of R&D, Oricell Therapeutics, Shanghai, 201203, People's Republic of China
| | - Xuhui Dong
- Department of R&D, Oricell Therapeutics, Shanghai, 201203, People's Republic of China
| | - Qirong Qian
- Department of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, People's Republic of China
| | - Shaorong Gao
- Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200120, People's Republic of China
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translation Research Center, Shanghai First Maternity and Infant Hospital, School of Life Science and Technology, Tongji University, Shanghai, 201204, People's Republic of China
- Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, 200092, People's Republic of China
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Deng X, Ye K, Tang J, Huang Y. Association of rs1800795 and rs1800796 polymorphisms in interleukin-6 gene and osteoarthritis risk: evidence from a meta-analysis. NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS 2023; 42:328-342. [PMID: 36395270 DOI: 10.1080/15257770.2022.2147541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Multiple studies have investigated the association of interleukin-6 (IL-6) gene polymorphisms and osteoarthritis (OA) risk, but failed to reach a consistent conclusion. Therefore, this study was designed to elucidate the association of IL-6 polymorphisms and OA by a meta-analysis approach. Literature retrieval was carried out on PubMed, EMBASE, Web of Science, CNKI, and Wanfang databases. The strength of association was appraised by odds ratios (ORs) and 95% confidence intervals (95%CIs) in five genetic models. The data were merged by using RevMan 5.3 software. Ten studies with 4944 cases and 4651 controls were analyzed. Overall, no significant association was identified between rs1800795 polymorphism and OA. Subgroup analysis by ethnicity and OA site also suggested rs1800795 polymorphism was not associated with OA. For rs1800796 polymorphism, G-allele and GG-genotype carriers appeared to have an increased risk to OA (G vs. C, OR = 1.66, 95%CI 1.30-1.96, P < 0.01; GG vs. CC, OR = 1.75, 95%CI 1.07-2.84, P = 0.03; GG vs. GC + CC, OR = 1.82, 95%CI 1.42-2.34, P < 0.01). Findings of this study indicate that the rs1800795 polymorphism is not correlated to OA susceptibility, regardless of ethnicity or OA site. However, rs1800796 polymorphism trends to be associated with susceptibility to OA.
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Affiliation(s)
- Xiaonan Deng
- Department of Orthopedic, Chengdu Xinhua Hospital Affiliated to North Sichuan Medical College, Chengdu, People's Republic of China
| | - Ke Ye
- Department of Orthopedic, Chengdu Xinhua Hospital Affiliated to North Sichuan Medical College, Chengdu, People's Republic of China
| | - Jidong Tang
- Department of Orthopedic, Chengdu Xinhua Hospital Affiliated to North Sichuan Medical College, Chengdu, People's Republic of China
| | - Yonghong Huang
- Department of Orthopedic, Chengdu Xinhua Hospital Affiliated to North Sichuan Medical College, Chengdu, People's Republic of China
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Yigit S, Tekcan A, Inanir A, Nursal AF, Akkanat S, Tural E. Effect of IL-6 -174G/C and -572G/C variants on susceptibility to osteoarthritis in Turkish population. NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS 2022; 42:65-76. [PMID: 35924736 DOI: 10.1080/15257770.2022.2107219] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/16/2022]
Abstract
Osteoarthritis (OA) is a complex disorder characterized by degenerative articular cartilage in which inflammatory mechanisms play a major role in the pathogenesis. Interleukin-6 (IL6), a multifunctional cytokine, can trigger osteoclast differentiation and bone resorption. Our purpose in this study was to evaluate the association of IL-6 -174 G/C (rs1800795) and -572 G/C (rs1800796) variants with the susceptibility to OA. One hundred fifty OA patients and 150 healthy individuals were enrolled in the study. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used for genotyping the IL-6 gene variants. The results of analyses were evaluated for statistical significance. The pain intensity was assessed using the Visual Analogue Scale (VAS). There was a statistically significant difference in the genotype and allele frequencies of the IL-6 -174 G/C variant between patients with OA and control groups (p = 0.001, p = 0.002, respectively). IL-6 -174 G/C GG genotype and G allele were more prevalent in patients with OA. We found that the IL-6 -572 G/C variant was not different between patients and controls in either genotype distribution and allele frequency. IL-6 174 G/C and -572 G/C loci GG-GG combined genotype was significantly higher in OA patients (p = 0.00). Our study suggests that there was a strong association between the IL-6 -174 G/C variant and OA in the Turkish population. Further studies on populations of different ethnic background are necessary to prove the association of IL-6 variants with OA.
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Affiliation(s)
- Serbulent Yigit
- Faculty of Veterinary, Department of Genetics, Ondokuz Mayıs University, Samsun, Turkey.,Faculty of Medicine, Department of Medical Biology, Gaziosmanpasa University, Tokat, Turkey
| | - Akin Tekcan
- Faculty of Medicine, Departments of Medical Biology, Amasya University, Amasya, Turkey
| | - Ahmet Inanir
- Dr. Ahmet Inanir Clinic, Kecioren, Ankara, Turkey
| | - Ayse Feyda Nursal
- Faculty of Medicine, Departments of Medical Genetics, Hitit University, Corum, Turkey
| | - Songul Akkanat
- Faculty of Medicine, Department of Medical Biology, Gaziosmanpasa University, Tokat, Turkey
| | - Ercan Tural
- Faculty of Health Sciences, Department of Physiotherapy and Rehabilitation, Ondokuz Mayıs University, Samsun, Turkey
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Singh M, Mastana S, Singh S, Juneja PK, Kaur T, Singh P. Promoter polymorphisms in IL-6 gene influence pro-inflammatory cytokines for the risk of osteoarthritis. Cytokine 2020; 127:154985. [DOI: 10.1016/j.cyto.2020.154985] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Revised: 12/31/2019] [Accepted: 01/02/2020] [Indexed: 11/28/2022]
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Chao C, Akileswaran L, Cooke Bailey JN, Willcox M, Van Gelder R, Lakkis C, Stapleton F, Richdale K. Potential Role of Ocular Microbiome, Host Genotype, Tear Cytokines, and Environmental Factors in Corneal Infiltrative Events in Contact Lens Wearers. Invest Ophthalmol Vis Sci 2019; 59:5752-5761. [PMID: 30516819 PMCID: PMC6281277 DOI: 10.1167/iovs.18-24845] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Purpose The purpose of this study was to explore differences in genotype, ocular surface microbiome, tear inflammatory markers, and environmental and behavioral exposures in soft contact lens (SCL) wearers with and without a history of corneal infiltrative events (CIEs). Methods Nine SCL wearers with a recent CIE and nine age-, sex-, and SCL material- and modality-matched controls were enrolled. The Contact Lens Risk Survey, slit-lamp examination data, basal tears, conjunctival microbial cultures, and peripheral blood samples were collected. Tear inflammatory mediator concentrations, genomic DNA from swabs, and whole exome sequencing of blood samples were quantified. Results There were no marked differences in SCL wear behaviors or exposures between case and control subjects. Predominant organisms detected among case and control subjects were Staphylococcus, Propionibacterium, Streptococcus, and Corynebacterium. Marginally higher levels of Neisseria were found in three of nine cases but zero of nine control samples (P = 0.056). A potentially deleterious missense single nucleotide polymorphism (SNP) variant in IL-6 Signal Transducer (IL6ST) was found in seven of eight cases and zero of nine controls (rs2228046; P = 0.03). The concentration of tear IL-6 was significantly higher in cases (4.5 [range, 2.1 to 6.2] pg/mL) versus controls (3.5 [range, 2.5 to 6.6] Pg/mL; = 0.02). Conclusions Tear IL-6 concentration was higher, and SNP variants were detected in subjects with a history of CIEs compared with healthy controls. The synthesis, signaling, and ocular surface cytokine concentration of IL-6 may be related to susceptibility to CIE. A larger study population is required to further explore relationships between genetic variations, the ocular surface microbiome, inflammatory mediators, and environmental exposures.
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Affiliation(s)
- Cecilia Chao
- Tufts Medical Center, Center for Translational Ocular Immunology, Boston, Massachusetts, United States.,University of New South Wales School of Optometry and Vision Science, Kensington, New South Wales, Australia
| | - Lakshmi Akileswaran
- Department of Ophthalmology, University of Washington Medical School, Seattle, Washington, United States
| | - Jessica N Cooke Bailey
- Department of Population and Quantitative Health Sciences, Case Western Reserve University, Institute for Computational Biology, Cleveland, Ohio, United States
| | - Mark Willcox
- University of New South Wales School of Optometry and Vision Science, Kensington, New South Wales, Australia
| | - Russell Van Gelder
- Department of Ophthalmology, University of Washington Medical School, Seattle, Washington, United States
| | - Carol Lakkis
- Johnson & Johnson Vision Care, Inc., Jacksonville, Florida, United States
| | - Fiona Stapleton
- University of New South Wales School of Optometry and Vision Science, Kensington, New South Wales, Australia
| | - Kathryn Richdale
- University of Houston College of Optometry, Houston, Texas, United States
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Eftekhari H, Hosseini SR, Pourreza Baboli H, Mafi Golchin M, Heidari L, Abedian Z, Pourbagher R, Amjadi-Moheb F, Mousavi Kani SN, Nooreddini H, Akhavan-Niaki H. Association of interleukin-6 (rs1800796) but not transforming growth factor beta 1 (rs1800469) with serum calcium levels in osteoporotic patients. Gene 2018; 671:21-27. [PMID: 29860063 DOI: 10.1016/j.gene.2018.05.118] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2018] [Revised: 05/20/2018] [Accepted: 05/30/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Osteoporosis is a multifactorial disease with a strong genetic influence. Recent studies have demonstrated that cytokines, such as TGF-β1 and interleukin 6 (IL-6) play complex roles in the normal bone metabolism and pathophysiology of osteoporosis. Here, we investigated the roles of 2 polymorphisms mapping to the promoters of TGF-β1and IL-6 genes on the genetic susceptibility to osteoporosis as well as calcium and vitamin D levels. METHODS A cohort of 297 elderly participants in northern Iran comprising 181 osteoporotic patients (mean age ± SD, 68.36 ± 7.21 years) and 116 unrelated healthy controls (mean age ± SD, 64 ± 5.44 years) was studied for TGF-β1(C-509T) and IL-6 (G-634C) polymorphisms using PCR-RFLP method. RESULTS A significant relationship was observed between calcium level and IL-6 genotypes in osteoporotic males (P = 0.011) and females (P = 0.020). No significant differences were observed between osteoporotic and control groups with respect to allele frequency or genotype distribution based on the 2 selected polymorphisms under different genetic models. The results remained the same after comparing the BMD values of either the femur neck or lumbar spine with the genotypes of the elderly men and women when analyzed separately. CONCLUSION IL-6 genotype influences serum calcium levels in osteoporotic patients. The lack of association between the common genetic variations of TGF-β1 and IL-6 genes, and BMD highlights the complex genetic background of osteoporosis in the north of Iran.
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Affiliation(s)
- Hajar Eftekhari
- Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran; Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Seyyed Reza Hosseini
- Social Determinants of Health (SDH) Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Hadis Pourreza Baboli
- Genetic Laboratory, Amirkola Children's Hospital, Babol University of Medical Sciences, Babol, Iran
| | - Maryam Mafi Golchin
- Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran; Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Laleh Heidari
- Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zeinab Abedian
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Roghayeh Pourbagher
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Fatemeh Amjadi-Moheb
- Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | | | - Hajighorban Nooreddini
- Department of Radiology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Haleh Akhavan-Niaki
- Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran; Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; Genetic Laboratory, Amirkola Children's Hospital, Babol University of Medical Sciences, Babol, Iran.
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Jeong J, Bae K, Kim SG, Kwak D, Moon YJ, Choi CH, Kim YR, Na CS, Kim SJ. Anti-osteoarthritic effects of ChondroT in a rat model of collagenase-induced osteoarthritis. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 18:131. [PMID: 29673343 PMCID: PMC5909276 DOI: 10.1186/s12906-018-2149-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/03/2017] [Accepted: 02/28/2018] [Indexed: 02/07/2023]
Abstract
Background Previously, we reported that ChondorT showed significant anti-arthritis and anti-inflammatory effects. ChondroT, a new herbal medication, consists of the water extracts of Osterici Radix, Lonicerae Folium, Angelicae Gigantis Radix, Clematidis Radix, and Phellodendri Cortex (6:4:4:4:3). The objective of this study was to investigate the effects of ChondroT in collagenase-induced osteoarthritis rat model. Methods Osteoarthritis was induced by the injection of collagenase into the right knee joint cavity of rats. The samples were divided into seven groups [intact (n = 6), control (n = 6), indomethacin (n = 6), Joins tab (n = 6), ChondroT50 (n = 6), ChondroT100 (n = 6), and ChondroT200 (n = 6)]. The control group was administered normal saline, indomethacin group was administered indomethacin (2 mg/kg), and Joins tab group was administered Joins Tab (20 mg/kg). The ChondroT50, ChondroT100, and ChondroT200 groups were administered 50, 100, and 200 mg/kg of ChondroT, respectively. All oral administrations were initiated 7 days after the induction of arthritis and were continued for a total of 12 days. At the end of the experiment, serum aminotransferase, albumin, blood urea nitrogen, creatinine, leukocyte, and inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6] were analyzed. Hematoxylin and eosin (H&E) and safranin O-fast green staining of the articular structures of the knee joint were performed. Results TNF-α and IL-1β decreased in the ChondroT100 and ChondroT200 groups compared with those in the control group. IL-6 and aspartate aminotransferase decreased in the ChondroT50, ChondroT100, and ChondroT200 groups compared with that in the control group. Albumin, WBC and lymphocytes decreased in the ChondroT100 and ChondroT200 groups compared with those in the control group. In H&E stain, synoviocytes, cartilage lacunae, and chondrocytes were well preserved in the ChondroT100 and ChondroT200 groups, and safranin O-fast staining showed a clear reaction of proteoglycans in the ChondroT100 and ChondroT200 groups. Conclusions Based on these results, it can be proposed that ChondroT has anti-osteoarthritic effects on collagenase-induced rat model.
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Zhan D, Thumtecho S, Tanavalee A, Yuktanandana P, Anomasiri W, Honsawek S. Association of adiponectin gene polymorphisms with knee osteoarthritis. World J Orthop 2017; 8:719-725. [PMID: 28979856 PMCID: PMC5605358 DOI: 10.5312/wjo.v8.i9.719] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Revised: 03/31/2017] [Accepted: 05/15/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the possible relationship of adiponectin (ADIPOQ) gene polymorphisms, plasma adiponectin, and the risk of knee osteoarthritis (OA).
METHODS A total of 398 subjects, 202 knee OA patients and 196 healthy individuals, were enrolled in the case-control study. Genotyping at +45T/G (rs2241766) and +276G/T (rs1501299) loci was performed using polymerase chain reaction-restriction fragment length polymorphism. Plasma adiponectin levels were assessed using enzyme-linked immunosorbent assay. OA severity was determined using the Kellgren-Lawrence (KL) grading system.
RESULTS No significant associations were observed in the genotype distributions and allele frequencies at two loci of +45T/G and +276G/T polymorphisms in the ADIPOQ between knee OA patients and control subjects. There was a significant association between genotype distribution of +276G/T polymorphism and KL grade 2, 3 or 4 (P = 0.037, P = 0.046, P = 0.016, respectively). At +45T/G locus, the percentage of GG genotype was notably greater in control subjects (13.40%) compared with OA subjects (1.70%) (P = 0.023). Plasma adiponectin was markedly decreased in OA subjects compared with control subjects (P = 0.03). Likewise, circulating adiponectin in OA subjects was notably lesser than that in control subjects in GG genotype of +45T/G (P = 0.029) and +276G/T polymorphisms (P = 0.012).
CONCLUSION Polymorphisms +45T/G and +276G/T of the ADIPOQ gene might not be responsible for OA susceptibility among Thais.
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Affiliation(s)
- Dong Zhan
- Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Suthimon Thumtecho
- Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Aree Tanavalee
- Vinai Parkpian Orthopaedic Research Center, Department of Orthopaedics, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Pongsak Yuktanandana
- Vinai Parkpian Orthopaedic Research Center, Department of Orthopaedics, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Wilai Anomasiri
- Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Sittisak Honsawek
- Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
- Vinai Parkpian Orthopaedic Research Center, Department of Orthopaedics, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
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Wang Y, Chu M, Rong J, Xing B, Zhu L, Zhao Y, Zhuang X, Jiang L. No association of the single nucleotide polymorphism rs8044769 in the fat mass and obesity-associated gene with knee osteoarthritis risk and body mass index: A population-based study in China. Bone Joint Res 2016; 5:169-74. [PMID: 27166265 PMCID: PMC4921048 DOI: 10.1302/2046-3758.55.2000589] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2015] [Accepted: 03/01/2016] [Indexed: 01/26/2023] Open
Abstract
OBJECTIVES Previous genome-wide association studies (GWAS) have reported significant association of the single nucleotide polymorphism (SNP) rs8044769 in the fat mass and obesity-associated gene (FTO) with osteoarthritis (OA) risk in European populations. However, these findings have not been confirmed in Chinese populations. METHODS We systematically genotyped rs8044769 and evaluated the association between the genetic variants and OA risk in a case-controlled study including 196 OA cases and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform. RESULTS We found that the variant T allele of rs8044769 showed no significant association of OA risk (p = 0.791), or association with body mass index (BMI) (pmeta = 0.786) in an additive genetic model. However, we detected a significant interaction between rs8044769 genotypes and BMI on OA risk (p = 0.037), as well as a borderline interaction between rs8044769 genotypes and age on OA risk (p = 0.062). CONCLUSIONS Our findings indicate that rs8044769 in the FTO gene may not modify individual susceptibility to OA or increased BMI in the Chinese population. Further studies are warranted to validate and extend our findings.Cite this article: Prof L. Jiang. No association of the single nucleotide polymorphism rs8044769 in the fat mass and obesity-associated gene with knee osteoarthritis risk and body mass index: A population-based study in China. Bone Joint Res 2016;5:169-174. DOI: 10.1302/2046-3758.55.2000589.
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Affiliation(s)
- Y Wang
- Department of Epidemiology, Nantong University, School of Public Health, Nantong, Jiangsu Province, China
| | - M Chu
- Department of Epidemiology, Nantong University, School of Public Health, Nantong, Jiangsu Province, China
| | - J Rong
- Department of Orthopedic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China
| | - B Xing
- Hongqi Community Health Service Center, Xiangfang District, Harbin, Heilongjiang Province, China
| | - L Zhu
- Department of Epidemiology, Public Health College, Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Y Zhao
- Department of Epidemiology, Public Health College, Harbin Medical University, Harbin, Heilongjiang Province, China
| | - X Zhuang
- Department of Epidemiology, Nantong University, School of Public Health, Nantong, Jiangsu Province, China
| | - L Jiang
- Department of Epidemiology, Nantong University, School of Public Health, Nantong, Jiangsu Province, China
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Abstract
BACKGROUND Obesity is associated with an increased risk of developing osteoarthritis (OA), even in non-weight bearing joints. High levels of adipose tissue-associated inflammation may explain this association. SOURCES OF DATA AND AREAS OF DEBATE Published evidence looking at the associations between components of Metabolic Syndrome (MetS) and knee, hip or hand OA and the higher mortality described with knee OA. EMERGING POINTS Development of MetS and OA shares a relationship with adipose tissue-associated inflammation. This review supports this inflammatory pathway being part of the shared mechanism behind obesity as a risk factor for OA and the recently described OA-associated increased mortality. TIMELY AREAS FOR DEVELOPMENT In an era of an obesity epidemic, this review identifies a need for well-designed cohort studies assessing early metabolic changes in populations at high risk of OA and MetS, and to identify risk factors for increased mortality in patients with OA.
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Affiliation(s)
- S Kluzek
- ARUK Sports, Exercise and Osteoarthritis Centre, University of Oxford, Oxford, UK Oxford NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK
| | - J L Newton
- ARUK Sports, Exercise and Osteoarthritis Centre, University of Oxford, Oxford, UK Oxford NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK The Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford OX3 7LD, UK
| | - N K Arden
- ARUK Sports, Exercise and Osteoarthritis Centre, University of Oxford, Oxford, UK Oxford NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK
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George SZ, Parr JJ, Wallace MR, Wu SS, Borsa PA, Dai Y, Fillingim RB. Inflammatory genes and psychological factors predict induced shoulder pain phenotype. Med Sci Sports Exerc 2015; 46:1871-81. [PMID: 24598699 DOI: 10.1249/mss.0000000000000328] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE The pain experience has multiple influences, but little is known about how specific biological and psychological factors interact to influence pain responses. The current study investigated the combined influences of genetic (pro-inflammatory) and psychological factors on several preclinical shoulder pain phenotypes. METHODS An exercise-induced shoulder injury model was used, and a priori selected genetic (IL1B, TNF/LTA region, and IL6 single nucleotide polymorphisms (SNP)) and psychological (anxiety, depression symptoms, pain catastrophizing, fear of pain, and kinesiophobia) factors were included as the predictors of interest. The phenotypes were pain intensity (5-d average and peak reported on numerical rating scale), upper extremity disability (5-d average and peak reported on the Quick Disabilities of the Arm, Shoulder and Hand instrument), and duration of shoulder pain (d). RESULTS After controlling for age, sex, and race, the genetic and psychological predictors were entered separately as main effects and interaction terms in regression models for each pain phenotype. Results from the recruited cohort (n = 190) indicated strong statistical evidence for the interactions between 1) TNF/LTA SNP rs2229094 and depression symptoms for average pain intensity and duration and 2) IL1B two SNP diplotype and kinesiophobia for average shoulder pain intensity. Moderate statistical evidence for prediction of additional shoulder pain phenotypes included interactions of kinesiophobia, fear of pain, or depressive symptoms with TNF/LTA rs2229094 and IL1B. CONCLUSIONS These findings support the combined predictive ability of specific genetic and psychological factors for shoulder pain phenotypes by revealing novel combinations that may merit further investigation in clinical cohorts to determine their involvement in the transition from acute to chronic pain conditions.
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Affiliation(s)
- Steven Z George
- 1Department of Physical Therapy, Center for Pain Research and Behavioral Health, University of Florida, Gainesville, FL; 2Department of Sports Medicine and Nutrition, University of Pittsburgh, Pittsburgh, PA; 3Department of Molecular Genetics and Microbiology, Center for Epigenetics, Genetics Institute, University of Florida, Gainesville, FL; 4Department of Biostatistics, University of Florida, Gainesville, FL; 5Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL; and 6Department of Community Dentistry and Behavioral Science, University of Florida, Gainesville, FL
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Abstract
The concept of meta-epidemiology has been introduced with considering the methodological limitations of systematic review for intervention trials. The paradigm of meta-epidemiology has shifted from a statistical method into a new methodology to close gaps between evidence and practice. Main interest of meta-epidemiology is to control potential biases in previous quantitative systematic reviews and draw appropriate evidences for establishing evidence-base guidelines. Nowadays, the network meta-epidemiology was suggested in order to overcome some limitations of meta-epidemiology. To activate meta-epidemiologic studies, implementation of tools for risk of bias and reporting guidelines such as the Consolidated Standards for Reporting Trials (CONSORT) should be done.
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Affiliation(s)
- Jong-Myon Bae
- Department of Preventive Medicine, Jeju National University School of Medicine, JeJu, Korea
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13
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Ni Y, Li H, Zhang Y, Zhang H, Pan Y, Ma J, Wang L. Association of IL-6 G-174C polymorphism with bone mineral density. J Bone Miner Metab 2014; 32:167-73. [PMID: 23760743 DOI: 10.1007/s00774-013-0477-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2012] [Accepted: 04/22/2013] [Indexed: 12/30/2022]
Abstract
Functional polymorphisms in the promoter region of interleukin-6 (IL-6) are known to be involved in bone mineral density (BMD) and the development of osteoporosis, but the reported results have been inconsistent. Using the meta-analysis approach, the present study is designed to provide a relatively comprehensive picture of the relationship between bone mineral density (BMD) or osteoporosis and polymorphisms in the promoter region of IL-6 (rs1800795 and rs1800796). The difference of bone mineral density (BMD) values between genotypes was examined by mean difference and 95 % confidence intervals (CIs). Association between IL-6 polymorphism and clinical osteoporosis was evaluated by pooled odds ratios (ORs) and 95 % CIs. A total of 13 articles with 11,499 subjects were included in the present study. For -174 (rs1800795), we found that individuals with the G/G genotype had a significantly lower BMD value than those with C/C genotype at femoral neck (0.02 g/cm(2), 95 % CI 0.00-0.03) (p = 0.04) and distal radius (0.01 g/cm(2), 95 %CI 0.01-0.01) (p < 0.0001). However, we did not find a statistically significant difference of BMD at the spine. When analysis was limited to postmenopausal women, similar results were obtained. We further found that the C/C genotype was associated with a reduced risk of osteoporosis compared to G/G genotype, and the pooled OR was 0.72 (95 % CI 0.54-0.95, p = 0.02). In addition, a significant relationship was found between G-634C (rs1800796) polymorphism and distal radius BMD (CC vs. GG: 0.02 g/cm(2), 95 % CI 0.01-0.03; GC vs. GG: 0.02 g/cm(2), 95 % CI 0.00-0.03) in the Asian population. These findings suggest that the CC genotype of IL-6 G-174C polymorphism may be associated with high BMD at femoral neck and distal radius and decreased risk of osteoporosis in the Caucasian population whereas G-634C polymorphism was associated with distal radius BMD in Asians.
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Affiliation(s)
- Yuanyuan Ni
- Institute of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, 210029, Jiangsu, China
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14
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Yao J, Feng XW, Yu XB, Xie HY, Zhu LX, Yang Z, Wei BJ, Zheng SS, Zhou L. Recipient IL-6-572C/G genotype is associated with reduced incidence of acute rejection following liver transplantation. J Int Med Res 2013; 41:356-64. [PMID: 23569034 DOI: 10.1177/0300060513477264] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
OBJECTIVE Acute rejection resulting from alloimmune responses is a major risk factor affecting patient survival following liver transplantation. Since interleukin (IL)-6 can mediate acute rejection, the association between IL-6 gene single nucleotide polymorphisms (SNPs) and incidence of acute rejection in liver transplant recipients was investigated. METHODS Patients who received liver transplant between January 2005 and December 2010 were typed for IL6-572C/G (rs1800796) polymorphisms using the snapshot technique. Association between genotype and acute rejection was analysed using the SNP Statistics website: http://bioinfo.iconcologia.net/snpstats/start.htm. Allelic and genotypic distributions for rs1800796 were compared among 335 patients with or without acute rejection within the first 6 months following liver transplant. RESULTS Incidence of acute rejection was 11.94%. A heterozygous CG genotype for IL6-572C/G was associated with a lower acute rejection rate compared with homozygous CC or GG genotypes. CONCLUSION IL6-572 CG genotype may be related to protection from acute rejection following liver transplant in Han Chinese patients.
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Affiliation(s)
- Jia Yao
- Division of Hepatobiliary and Pancreatic Surgery, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
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15
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Zhang H, Xu Y, Li L, Liu R, Ma B. The interleukin-6 -174G/C polymorphism and prostate cancer risk: a systematic review and meta-analysis. Urol Int 2012; 88:447-53. [PMID: 22516897 DOI: 10.1159/000335207] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2011] [Accepted: 11/20/2011] [Indexed: 01/05/2023]
Abstract
OBJECTIVE This systematic review and meta-analysis was undertaken to integrate previous findings and summarize the effect size of the association of interleukin-6 (IL-6) genetic polymorphism -174G/C with susceptibility to prostate cancer (PCa). METHODS All eligible studies of IL-6 -174G/C polymorphism and PCa risk were collected from the following electronic databases: PubMed and the Cochrane Library, with the last report up to June 1, 2011. Statistical analyses were performed by Review Manage version 5.0 and Stata 10.0. RESULTS A total of 7 independent studies, including 9,959 cases and 12,361 controls, were identified. When all studies were pooled, we did not detect a significant association of -174G/C polymorphism with PCa risk. When stratifying for race, similar results were obtained; evidence of a significant relation was absent in both Caucasians and the mixed population. After stratifying the studies by study types, -174G/C polymorphism was significantly associated with PCa risk when examining the contrast of CC + GC versus GG (OR = 1.44, 95% CI = 1.05-1.98, p = 0.03) in cohort studies but not in case-control studies. CONCLUSIONS Our review suggest that -174G/C polymorphism is associated with an increased PCa risk in two cohort studies from one article. Additional well-designed studies are warranted to validate these findings.
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Affiliation(s)
- Hongtuan Zhang
- Department of Urology, Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin, PR China
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16
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Honsawek S, Malila S, Yuktanandana P, Tanavalee A, Deepaisarnsakul B, Parvizi J. Association of MMP-3 (-1612 5A/6A) polymorphism with knee osteoarthritis in Thai population. Rheumatol Int 2012; 33:435-9. [PMID: 22457004 DOI: 10.1007/s00296-012-2371-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2011] [Accepted: 03/11/2012] [Indexed: 12/30/2022]
Abstract
Osteoarthritis (OA) is a degenerative joint disorder resulting in destruction of articular cartilage, osteophyte formation, and subchondral bone sclerosis. In recent years, numerous genetic factors have been identified and implicated in causing osteoarthritis. One such genetic defect is a single nucleotide polymorphism at position -1612 of matrix metalloproteinase-3 (MMP-3) promoter region, known to lead to three possible genotypes, 5A/5A, 6A/6A, and 5A/6A. The purpose of this study was to investigate the association of MMP-3 -1612 5A/6A gene polymorphism with knee osteoarthritis in Thai population. Genotype distributions and allelic frequencies of MMP-3 -1612 5A/6A polymorphism were investigated in 200 participants (100 patients with knee osteoarthritis and 100 healthy controls). Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism. There was no statistically significant difference between the groups with respect to genotype distribution (P > 0.05). The 5A allele frequency was indicated as 15.5 %, and 6A allele was as 84.5 % in OA patients, whereas it was 10-90 % in the control group. Accordingly, the present study has indicated that the -1612 5A/6A polymorphism genotypes of MMP-3 gene promoter do not play a role in the development of osteoarthritis in the Thai population.
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Affiliation(s)
- Sittisak Honsawek
- Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
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17
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Abstract
Type 1 diabetes (T1D) is one of the most widely studied complex genetic disorders, and the genes in HLA are reported to account for approximately 40-50% of the familial aggregation of T1D. The major genetic determinants of this disease are polymorphisms of class II HLA genes encoding DQ and DR. The DR-DQ haplotypes conferring the highest risk are DRB1*03:01-DQA1*05:01-DQB1*02:01 (abbreviated "DR3") and DRB1*04:01/02/04/05/08-DQA1*03:01-DQB1*03:02/04 (or DQB1*02; abbreviated "DR4"). The risk is much higher for the heterozygote formed by these two haplotypes (OR = 16.59; 95% CI, 13.7-20.1) than for either of the homozygotes (DR3/DR3, OR = 6.32; 95% CI, 5.12-7.80; DR4/DR4, OR = 5.68; 95% CI, 3.91). In addition, some haplotypes confer strong protection from disease, such as DRB1*15:01-DQA1*01:02-DQB1*06:02 (abbreviated "DR2"; OR = 0.03; 95% CI, 0.01-0.07). After adjusting for the genetic correlation with DR and DQ, significant associations can be seen for HLA class II DPB1 alleles, in particular, DPB1*04:02, DPB1*03:01, and DPB1*02:02. Outside of the class II region, the strongest susceptibility is conferred by class I allele B*39:06 (OR =10.31; 95% CI, 4.21-25.1) and other HLA-B alleles. In addition, several loci in the class III region are reported to be associated with T1D, as are some loci telomeric to class I. Not surprisingly, current approaches for the prediction of T1D in screening studies take advantage of genotyping HLA-DR and HLA-DQ loci, which is then combined with family history and screening for autoantibodies directed against islet-cell antigens. Inclusion of additional moderate HLA risk haplotypes may help identify the majority of children with T1D before the onset of the disease.
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Affiliation(s)
- Janelle A Noble
- Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
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18
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Lv C, Xu X, Wang J, Zhang Z, Zhang D, Guo C, Geng C, Sun Y. Combined effect of cytokine gene polymorphisms on end-stage knee osteoarthritis from Chinese Han population. Rheumatol Int 2011; 32:3625-9. [PMID: 22119941 DOI: 10.1007/s00296-011-2169-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2011] [Accepted: 10/18/2011] [Indexed: 11/30/2022]
Abstract
The mechanism of osteoarthritis (OA) is not well understood. Cytokines have been implicated in the episode, and there is increasing evidence that the host's cytokine response is genetically determined. We determined the predictive value of IL-634G./C, ICAM-1 469 K/E and IL-10-1082A/G, -819T/C and -592A/C gene polymorphisms on knee OA. The study included 1007 patients with end-stage knee OA and 910 healthy controls. Genomic DNA was prepared from peripheral blood leukocytes. Genotypes and allele frequencies were determined using restriction fragment length polymorphism analysis of polymerase chain reaction products. No significant difference in the IL-10 promoter allele or haplotype frequencies between end-stage knee OA and controls was found. Patients with end-stage knee OA showed a significantly higher prevalence of IL-6-634G/ICAM-1 469E carrier than that in controls (P = 0.017). Results indicate that IL-6-634G/ICAM-1 469E carrier could be associated with increased susceptibility to end-stage knee OA.
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Affiliation(s)
- Chengyu Lv
- Department of Joint Surgery, Associated Hospital of Qingdao University Medical College, 16 Jiangsu Road, Qingdao, Shandong Province, 266003, People's Republic of China.
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19
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Lack of an association between interleukin-6 gene promoter polymorphisms (−174G/C, −572G/C) and ischemic heart disease and/or ischemic stroke: A meta-analysis. Hum Immunol 2011; 72:641-51. [DOI: 10.1016/j.humimm.2011.03.019] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2010] [Revised: 03/03/2011] [Accepted: 03/31/2011] [Indexed: 01/17/2023]
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20
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Valdes AM, Evangelou E, Kerkhof HJM, Tamm A, Doherty SA, Kisand K, Tamm A, Kerna I, Uitterlinden A, Hofman A, Rivadeneira F, Cooper C, Dennison EM, Zhang W, Muir KR, Ioannidis JPA, Wheeler M, Maciewicz RA, van Meurs JB, Arden NK, Spector TD, Doherty M. The GDF5 rs143383 polymorphism is associated with osteoarthritis of the knee with genome-wide statistical significance. Ann Rheum Dis 2011; 70:873-5. [PMID: 20870806 PMCID: PMC4699799 DOI: 10.1136/ard.2010.134155] [Citation(s) in RCA: 114] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Affiliation(s)
- Ana M Valdes
- Department of Twin Research and Genetic Epidemiology Unit, St Thomas’ Hospital, King’s College London, London, UK
| | - Evangelos Evangelou
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | - Hanneke J M Kerkhof
- Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
- Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands
| | - Agu Tamm
- Department of Internal Medicine, University of Tartu, Tartu, Estonia
| | - Sally A Doherty
- Academic Rheumatology, University of Nottingham, City Hospital Nottingham, Nottingham, UK
| | - Kalle Kisand
- Department of Internal Medicine, University of Tartu, Tartu, Estonia
- Immunology Group, Institute of General and Molecular Pathology, University of Tartu, Tartu, Estonia
| | - Ann Tamm
- Department of Sports Medicine and Rehabilitation, University of Tartu, Tartu, Estonia
| | - Irina Kerna
- Department of Internal Medicine, University of Tartu, Tartu, Estonia
| | - Andre Uitterlinden
- Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
- Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands
| | - Albert Hofman
- Department of Sports Medicine and Rehabilitation, University of Tartu, Tartu, Estonia
| | - Fernando Rivadeneira
- Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
- Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands
| | - Cyrus Cooper
- MRC Epidemiology Resource Centre, Southampton, UK
- Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK
| | | | - Weiya Zhang
- Academic Rheumatology, University of Nottingham, City Hospital Nottingham, Nottingham, UK
| | - Kenneth R Muir
- Health Sciences Research Institute, Warwick Medical School, University of Warwick, Warwick, UK
| | - John P A Ioannidis
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | - Margaret Wheeler
- Academic Rheumatology, University of Nottingham, City Hospital Nottingham, Nottingham, UK
| | - Rose A Maciewicz
- Respiratory and Inflammation Research Area, AstraZeneca, Charnwood R&D, Loughborough, UK
| | - Joyce B van Meurs
- Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
- Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands
| | - Nigel K Arden
- MRC Epidemiology Resource Centre, Southampton, UK
- Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK
| | - Tim D Spector
- Department of Twin Research and Genetic Epidemiology Unit, St Thomas’ Hospital, King’s College London, London, UK
| | - Michael Doherty
- Academic Rheumatology, University of Nottingham, City Hospital Nottingham, Nottingham, UK
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21
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Kerkhof HJ, Meulenbelt I, Akune T, Arden NK, Aromaa A, Bierma-Zeinstra SM, Carr A, Cooper C, Dai J, Doherty M, Doherty SA, Felson D, Gonzalez A, Gordon A, Harilainen A, Hart DJ, Hauksson VB, Heliovaara M, Hofman A, Ikegawa S, Ingvarsson T, Jiang Q, Jonsson H, Jonsdottir I, Kawaguchi H, Kloppenburg M, Kujala UM, Lane NE, Leino-Arjas P, Lohmander S, Luyten FP, Malizos KN, Nakajima M, Nevitt MC, Pols HA, Rivadeneira F, Shi D, Slagboom E, Spector TD, Stefansson K, Sudo A, Tamm A, Tamm AE, Tsezou A, Uchida A, Uitterlinden AG, Wilkinson JM, Yoshimura N, Valdes AM, van Meurs JB. Recommendations for standardization and phenotype definitions in genetic studies of osteoarthritis: the TREAT-OA consortium. Osteoarthritis Cartilage 2011; 19:254-64. [PMID: 21059398 PMCID: PMC3236091 DOI: 10.1016/j.joca.2010.10.027] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2010] [Revised: 10/15/2010] [Accepted: 10/26/2010] [Indexed: 02/02/2023]
Abstract
OBJECTIVE To address the need for standardization of osteoarthritis (OA) phenotypes by examining the effect of heterogeneity among symptomatic (SOA) and radiographic osteoarthritis (ROA) phenotypes. METHODS Descriptions of OA phenotypes of the 28 studies involved in the TREAT-OA consortium were collected. We investigated whether different OA definitions result in different association results by creating various hip OA definitions in one large population based cohort (the Rotterdam Study I (RSI)) and testing those for association with gender, age and body mass index using one-way ANOVA. For ROA, we standardized the hip-, knee- and hand ROA definitions and calculated prevalence's of ROA before and after standardization in nine cohort studies. This procedure could only be performed in cohort studies and standardization of SOA definitions was not feasible at this moment. RESULTS In this consortium, all studies with SOA phenotypes (knee, hip and hand) used a different definition and/or assessment of OA status. For knee-, hip- and hand ROA five, four and seven different definitions were used, respectively. Different hip ROA definitions do lead to different association results. For example, we showed in the RSI that hip OA defined as "at least definite joint space narrowing (JSN) and one definite osteophyte" was not associated with gender (P =0.22), but defined as "at least one definite osteophyte" was significantly associated with gender (P=3×10(-9)). Therefore, a standardization process was undertaken for ROA definitions. Before standardization a wide range of ROA prevalence's was observed in the nine cohorts studied. After standardization the range in prevalence of knee- and hip ROA was small. CONCLUSION Phenotype definitions influence the prevalence of OA and association with clinical variables. ROA phenotypes within the TREAT-OA consortium were standardized to reduce heterogeneity and improve power in future genetics studies.
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Affiliation(s)
- Hanneke J.M. Kerkhof
- Department of Internal Medicine, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands,The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Rotterdam/Leiden, the Netherlands
| | - Ingrid Meulenbelt
- The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Rotterdam/Leiden, the Netherlands,Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Toru Akune
- Department of Clinical Motor System Medicine, 22nd Century Medical and Research Center, The University of Tokyo, Tokyo, Japan
| | - Nigel K. Arden
- MRC Epidemiology Resource Centre University of Southampton, Southampton General Hospital, Southampton, United Kingdom,NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford England Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences University of Oxford, Oxford, United Kingdom
| | - Arpo Aromaa
- The National Institute for Health and Welfare (THL), Helsinki, Finland
| | | | - Andrew Carr
- NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford England Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences University of Oxford, Oxford, United Kingdom
| | - Cyrus Cooper
- MRC Epidemiology Resource Centre University of Southampton, Southampton General Hospital, Southampton, United Kingdom,NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford England Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences University of Oxford, Oxford, United Kingdom
| | - Jin Dai
- Center of Diagnosis and Treatment for Joint Disease, Nanjing DrumTower Hospital, The affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Michael Doherty
- Academic Rheumatology, Clinical Sciences Building, Nottingham City Hospital Hucknall Road, Nottingham, United Kingdom
| | - Sally A. Doherty
- Academic Rheumatology, Clinical Sciences Building, Nottingham City Hospital Hucknall Road, Nottingham, United Kingdom
| | - David Felson
- Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, MA, United States of America
| | - Antonio Gonzalez
- Laboratorio Investigacion and Rheumatology Unit, Hospital Clinico Universitario Santiago, Santiago de Compostela, Spain
| | - Andrew Gordon
- Academic Unit of Bone Metabolism, Department of Human Metabolism, University of Sheffield, Sheffield, United Kingdom,Sheffield NIHR Bone Biomedical research Unit, Centre for Biomedical Research, Northern General Hospital, Sheffield, United Kingdom
| | - Arsi Harilainen
- ORTON Orthopedic Hospital, Invalid Foundation, Helsinki, Finland
| | - Deborah J. Hart
- Department of Twin Research and Genetic Epidemiology, St. Thomas' Hospital, King's College London, London, United Kingdom
| | | | - Markku Heliovaara
- The National Institute for Health and Welfare (THL), Helsinki, Finland
| | - Albert Hofman
- The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Rotterdam/Leiden, the Netherlands,Department of Epidemiology, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Shiro Ikegawa
- Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, Japan
| | - Thorvaldur Ingvarsson
- FSA University Hospital, Institution of Health Science, University of Akureyri, Akureyri, Iceland
| | - Qing Jiang
- Center of Diagnosis and Treatment for Joint Disease, Nanjing DrumTower Hospital, The affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Helgi Jonsson
- Department of Medicine, Landspitali University Hospital and Faculty of Medicine, University of Iceland, Reykjavik, Iceland
| | - Ingileif Jonsdottir
- deCODE Genetics, Reykjavik, Iceland,Department of Medicine, Landspitali University Hospital and Faculty of Medicine, University of Iceland, Reykjavik, Iceland
| | - Hiroshi Kawaguchi
- Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Margreet Kloppenburg
- Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands
| | - Urho M. Kujala
- Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland
| | - Nancy E. Lane
- University of California at San Francisco and University of California at Davis, Sacramento, United States of America
| | | | - Stefan Lohmander
- Department of Orthopedics, Clinical Sciences, Lund University, Lund, Sweden
| | - Frank P. Luyten
- Laboratory for Skeletal Development and Joint Disorders, Division of Rheumatology, Katholieke Universiteit Leuven, Belgium
| | | | - Masahiro Nakajima
- Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, Japan
| | - Michael C. Nevitt
- University of California at San Francisco and University of California at Davis, Sacramento, United States of America
| | - Huibert A.P. Pols
- Department of Internal Medicine, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Fernando Rivadeneira
- Department of Internal Medicine, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands,The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Rotterdam/Leiden, the Netherlands,Department of Epidemiology, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Dongquan Shi
- Center of Diagnosis and Treatment for Joint Disease, Nanjing DrumTower Hospital, The affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Eline Slagboom
- The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Rotterdam/Leiden, the Netherlands,Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Tim D. Spector
- Department of Twin Research and Genetic Epidemiology, St. Thomas' Hospital, King's College London, London, United Kingdom
| | - Kari Stefansson
- deCODE Genetics, Reykjavik, Iceland,Department of Medicine, Landspitali University Hospital and Faculty of Medicine, University of Iceland, Reykjavik, Iceland
| | - Akihiro Sudo
- Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Japan
| | - Agu Tamm
- Department of Internal Medicine, University of Tartu, Estonia
| | - Ann E. Tamm
- Department of Sport Medicine and Rehabilitation, Univerity of Tartu, Estonia
| | - Aspasia Tsezou
- Department of Biology and Genetics, University of Thessaly, Larissa, Greece
| | - Atsumasa Uchida
- Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Japan
| | - André G. Uitterlinden
- Department of Internal Medicine, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands,The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Rotterdam/Leiden, the Netherlands,Department of Epidemiology, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Jeremy Mark Wilkinson
- Academic Unit of Bone Metabolism, Department of Human Metabolism, University of Sheffield, Sheffield, United Kingdom,Sheffield NIHR Bone Biomedical research Unit, Centre for Biomedical Research, Northern General Hospital, Sheffield, United Kingdom
| | - Noriko Yoshimura
- Department of Joint Disease Research, 22nd Century Medical and Research Center, The University of Tokyo Hospital, The University of Tokyo, Tokyo, Japan
| | - Ana M. Valdes
- Department of Twin Research and Genetic Epidemiology, St. Thomas' Hospital, King's College London, London, United Kingdom
| | - Joyce B.J. van Meurs
- Department of Internal Medicine, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands,The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Rotterdam/Leiden, the Netherlands
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22
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Abstract
Osteoarthritis (OA) is the most common cause of arthritis and represents an enormous healthcare burden in industrialized societies. Current therapeutic approaches for OA are limited and are insufficient to prevent the initiation and progression of the disease. Genetic studies of patients with OA can help to unravel the molecular mechanisms responsible for specific disease manifestations, including joint damage, nociception and chronic pain. Indeed, these studies have identified molecules, such as growth/differentiation factor 5, involved in signaling cascades that are important for the pathology of joint components. Genome-wide association studies have uncovered a likely role in OA for the genes encoding structural extracellular matrix components (such as DVWA) and molecules involved in prostaglandin metabolism (such as DQB1 and BTNL2). A ∼300 kilobase region in chromosome 7q22 is also associated with OA susceptibility. Finally, the identification of individuals at a high risk of OA and of total joint arthroplasty failure might be facilitated by the use of combinations of genetic markers, allowing for the application of preventive and disease-management strategies.
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