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Szymczak-Tomczak A, Kaczmarek-Ryś M, Hryhorowicz S, Michalak M, Eder P, Skrzypczak-Zielińska M, Łykowska-Szuber L, Tomczak M, Słomski R, Dobrowolska A, Krela-Kaźmierczak I. Vitamin D, Vitamin D Receptor (VDR) Gene Polymorphisms (ApaI and FokI), and Bone Mineral Density in Patients With Inflammatory Bowel Disease. J Clin Densitom 2021; 24:233-242. [PMID: 33172802 DOI: 10.1016/j.jocd.2020.10.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 10/18/2020] [Accepted: 10/20/2020] [Indexed: 02/06/2023]
Abstract
In the etiology of inflammatory bowel disease (IBD) and osteoporosis, the connecting element is the involvement of environmental and genetic factors. Vitamin D receptor (VDR) gene polymorphisms may be associated with the pathogenesis of IBD and bone mineral density (BMD). The study aimed to analyze the relationship between ApaI and FokI polymorphisms of the VDR gene, serum vitamin D concentration, and BMD in patients with IBD. The studied group consisted of 172 patients (85 with Crohn's disease [CD], 87 with ulcerative colitis [UC], and 39 healthy subjects - control group [CG]) were examined. Lumbar spine densitometry (L1-L4) and the femoral neck (FN) measurements were performed using dual-energy X-ray absorptiometry (DXA). Serum concentrations of 25-hydroxyvitamin D were determined using electrochemiluminescence binding assay (ECLIA). Polymorphisms were determined with polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). . We found no statistically significant differences in vitamin D concentration between the 3 studied groups. CD patients who were FF homozygotes had significantly lower FN BMD than FF homozygous from CG (p-value < 0.05). CD patients who were Aa heterozygotes had significantly lower lumbar spine (L2-L4) BMD than Aa heterozygotes from CG (p-value < 0.05). Among patients with the same polymorphic variants, but belonging to different studied groups, statistically significant differences in bone mineral density in the lumbar spine and the closer end of the femoral neck were observed. We consider that it is the disease entity, not the polymorphism variant, may have a decisive impact on BMD.
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Affiliation(s)
- Aleksandra Szymczak-Tomczak
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
| | | | | | - Michał Michalak
- Department of Computer Sciences and Statistics, Poznan University of Medical Sciences, Poznan, Poland
| | - Piotr Eder
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
| | | | - Liliana Łykowska-Szuber
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
| | - Maciej Tomczak
- Department of Psychology, Poznan University of Physical Education, Poland
| | - Ryszard Słomski
- Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland
| | - Agnieszka Dobrowolska
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
| | - Iwona Krela-Kaźmierczak
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland.
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Rigoli L, Caruso RA. Inflammatory bowel disease in pediatric and adolescent patients: A biomolecular and histopathological review. World J Gastroenterol 2014; 20:10262-10278. [PMID: 25132743 PMCID: PMC4130834 DOI: 10.3748/wjg.v20.i30.10262] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2013] [Revised: 01/13/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
Crohn’s disease (CD) and ulcerative colitis (UC) are the two main forms of inflammatory bowel disease (IBD) with both overlapping and distinct clinical, pathological and biomolecular features. It has been suggested that pediatric IBD is a distinct disease entity, with probably different disease subtypes.The aim of this study is to review and summarize the evolution of the current concept of pediatric IBD. The results of this review reinforce the idea that pediatric CD and UC may be further classified in various clinicopathologic entities. For clinicians and pathologists convenience, practical algorithms for the distinction of the various subphenotypes of pediatric IBD are also provided.
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Hlavaty T, Toth J, Koller T, Krajcovicova A, Oravcova S, Zelinkova Z, Huorka M. Smoking, breastfeeding, physical inactivity, contact with animals, and size of the family influence the risk of inflammatory bowel disease: A Slovak case-control study. United European Gastroenterol J 2014; 1:109-19. [PMID: 24917948 DOI: 10.1177/2050640613478011] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2012] [Accepted: 01/16/2013] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The aetiology of inflammatory bowel disease (IBD) is not known but is likely to involve a combination of genetic predisposition and environmental risk factors. Smoking has been associated consistently with a higher risk of Crohn's disease (CD), while appendectomy and smoking appear to diminish the risk of ulcerative colitis (UC). The roles of other environmental factors are unclear. The aim of the present study was to evaluate the association of CD and UC with several environmental risk factors. METHODS This case-control study included 338 patients (190 CD, 148 UC) and 355 controls. All subjects completed a detailed questionnaire regarding breastfeeding duration, history of helminthic infections, allergic diseases, appendectomy, household size, housing type, contact with specific domestic animals, physical activity, and smoking. Associations between risk factors and CD and UC were investigated by univariate and multivariate analysis. RESULTS On multivariate analysis, CD associated with smoking at diagnosis (odds ratio, OR, 3.7, 95% CI 2.2-6.2; p < 0.001), being breastfed for <6 months (OR 2.7, 95% CI 1.7-4.4; p < 0.001), and less than two childhood sporting activities weekly (OR 2.7, 95% CI 1.5-5.0; p < 0.001) and inversely associated with frequent contact with cats in childhood (OR 0.6, 95% CI 0.4-0.9; p < 0.03). UC associated with less than two sporting weekly activities in childhood (OR 2.0, 95% CI 1.1-3.5, p = 0.02), fewer household members in childhood (OR 0.8, 95% CI 0.7-0.98, p = 0.03), and being breastfed for <6 months (OR 1.7, 95% CI 1.02-2.8, p = 0.04). A composite environmental risk index for CD revealed that 47 and 14% of the controls and patients with CD had no risk factors, respectively, and that 14 and 38% of the controls and patients with CD had at least two risk factors, respectively. CONCLUSION CD and UC associated with infrequent childhood sports activities and short breastfeeding. Furthermore, CD associated with smoking and infrequent contact with animals in childhood. UC associated with a smaller family size in childhood.
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Affiliation(s)
- Tibor Hlavaty
- University Hospital Bratislava, Bratislava, Slovakia
| | - Jozef Toth
- University Hospital Bratislava, Bratislava, Slovakia
| | - Tomas Koller
- University Hospital Bratislava, Bratislava, Slovakia
| | | | | | | | - Martin Huorka
- University Hospital Bratislava, Bratislava, Slovakia
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Kosmidou M, Mpolotsis V, Christou L, Tsianos EV. Late onset of Crohn’s disease in familial Mediterranean fever: the necessity of anti-TNF treatment. J Dig Dis 2014; 15:102-4. [PMID: 24734305 DOI: 10.1111/1751-2980.12109] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Abstract
BACKGROUND Association of NOD2 (CARD15) gene mutations with inflammatory bowel diseases (IBD) is well known. We herein aimed to investigate the role of familial Mediterranean fever-associated MEFV variations in IBD patients as additional regional-specific risk factor. STUDY One hundred thirty-seven (78 female, 56.9%) IBD patients [62 Crohn's disease (CD), 75 ulcerative colitis (UC)] were enrolled into the study. The diagnosis of all patients was confirmed by colonoscopy, histopathology, and the clinical findings. One hundred one healthy donors' samples were used as healthy controls. All patients were genotyped for the most common E148Q, M608I, M694V, and V726A variations of the MEFV and R702W, G908R, and 1007fs of the NOD2. RESULTS The overall MEFV variation frequency was found to be higher in the IBD (25.5%) patients (28% in UC, 22.6% in CD) compared with controls (9.9%, P=0.006). This association was stronger with the penetrant exon 10 variations (M694V, M680I, V726A; odds ratio =4.5, P=0.001). Contribution of M694V was higher compared with the other variations (14.5% in CD, 17.3% in UC and 3% in controls, odds ratio =6.039, 95% confidence intervals, 1.7-20.7, P=0.002). The overall frequency of 3 NOD2 variants in the IBD group was not different from that of controls. CONCLUSIONS The results of this study suggest that the MEFV variations may be an additional susceptibility factor for IBD in certain parts of the world where the carrier rate is high, and the genetic background of the IBD patients may show regional changes.
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Di Sabatino A, Rovedatti L, Vidali F, Macdonald TT, Corazza GR. Recent advances in understanding Crohn's disease. Intern Emerg Med 2013; 8:101-13. [PMID: 21553239 DOI: 10.1007/s11739-011-0599-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2011] [Accepted: 04/19/2011] [Indexed: 12/19/2022]
Abstract
Crohn's disease is a chronic inflammatory bowel disorder resulting from an inappropriate innate and acquired immune response to commensal microorganisms in genetically susceptible individuals. This disease has a fluctuating course, with alternating periods of remission and relapses, and it is characterized by a remarkable clinical heterogeneity; it may be complicated by perianal fistulas, abscesses, and intestinal strictures leading to obstructions, besides several systemic manifestations. However, a complete resolution of the disease is currently not possible, yet Crohn's disease can be managed with established and novel therapies, which achieve long-term remission and acceptable quality of life. This review is focused on novel advances in basic and clinical aspects of Crohn's disease, although it also deals with new trends in diagnosis and treatment.
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Affiliation(s)
- Antonio Di Sabatino
- First Department of Medicine, Centro per lo Studio e la Cura delle Malattie Infiammatorie Croniche Intestinali, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy.
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Maiti AK, Nath SK. Gene network analysis of small molecules with autoimmune disease associated genes predicts a novel strategy for drug efficacy. Autoimmun Rev 2012; 12:510-22. [PMID: 23000205 DOI: 10.1016/j.autrev.2012.09.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2012] [Accepted: 09/10/2012] [Indexed: 02/09/2023]
Abstract
Numerous genes/SNPs in autoimmune diseases (ADs) are identified through genome-wide association studies (GWAS) and likely to contribute in developing autoimmune phenotypes. Constructions of biologically meaningful pathways are necessary to determine how these genes interact with each other and with other small molecules to develop various complex AD phenotypes prior to beginning time-consuming rigorous experimentation. We have constructed biological pathways with genetically identified genes leading to shared AD phenotypes. Various environmental and endogenous factors interact with these AD associated genes suggesting their critical role in developing diseases and further association studies could be designed for assessing the role of these factors with risk allele in a specific gene. Additionally, existing drugs that have been used long before the identification of these genetically associated genes also interact with these newly associated genes. Thus advanced therapeutic strategies could be designed by grouping patients with risk allele(s) in particular genes that directly or closely interact with the specified drugs. This drug-susceptible gene network will not only increase our understanding about the additional molecular basis for effectiveness against these diseases but also indicate which drug could be more effective for those patients carrying risk allele(s) in that gene. Additionally, we have also identified several interlinking genes in the pathways that could be used for designing future association studies.
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Affiliation(s)
- Amit K Maiti
- Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, 825 N.E. 13th Street, Oklahoma City, OK 73104, United States.
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Abbasian J, Martin TM, Patel S, Tessler HH, Goldstein DA. Immunologic and genetic markers in patients with idiopathic ocular inflammation and a family history of inflammatory bowel disease. Am J Ophthalmol 2012; 154:72-7. [PMID: 22464367 DOI: 10.1016/j.ajo.2012.01.016] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2011] [Revised: 01/15/2012] [Accepted: 01/16/2012] [Indexed: 12/19/2022]
Abstract
PURPOSE To evaluate the prevalence of immunologic and genetic markers in patients with idiopathic ocular inflammation and a family history of inflammatory bowel disease. DESIGN Matched case-control study. METHODS Patients with a diagnosis of idiopathic ocular inflammation and family history of inflammatory bowel disease who did not have inflammatory bowel disease themselves were identified and matched to control patients with idiopathic ocular inflammation. Serum was evaluated for immunologic markers using Prometheus IBD Serology 7. Genomic DNA was analyzed for single nucleotide polymorphisms (SNP) of the NOD2 gene associated with Crohn disease. RESULTS Fifteen patients with idiopathic ocular inflammation and family history of inflammatory bowel disease were matched to 15 control patients based on age, sex, and race. Eight of 15 patients (53%) with a family history of inflammatory bowel disease had elevated p-ANCA antibody levels compared to 3 of 15 controls (20%) (1-sided P = .04) with a matched analysis odds ratio of 6.0 (1-sided P = .06). Four of 15 patients (27%) with family history of inflammatory bowel disease tested positive for immunologic markers predicting ulcerative colitis, while no control patients tested positive (1-sided P = .06). Carrier rates of NOD2 SNPs did not differ significantly between the test and control groups. CONCLUSIONS One-quarter of patients with idiopathic ocular inflammation and a family history of inflammatory bowel disease had immunologic markers predicting bowel disease, and one-half had elevated p-ANCA levels. Prometheus IBD Serology 7 may be useful in the evaluation of selected patients with unexplained uveitis.
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Sehgal R, Berg A, Polinski JI, Hegarty JP, Lin Z, McKenna KJ, Stewart DB, Poritz LS, Koltun WA. Mutations in IRGM are associated with more frequent need for surgery in patients with ileocolonic Crohn's disease. Dis Colon Rectum 2012; 55:115-21. [PMID: 22228152 DOI: 10.1097/dcr.0b013e31823ccea8] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND There are no clear criteria for judging the severity of disease in patients with Crohn's disease. Yet classification of patients into low- and high-risk severity groups would benefit both medical and surgical management. At the time of this study, approximately 80 single-nucleotide polymorphisms within 55 genes had been associated with IBD. OBJECTIVE The aim of this study was to identify genetic determinants (single-nucleotide polymorphisms) that could be markers of Crohn's disease severity by the use of frequency of ileocolic surgery as a surrogate for disease severity. DESIGN Sixty-six patients (30 male) with ileocolonic Crohn's disease who previously underwent ileocolectomy were retrospectively studied. The severity of Crohn's disease was quantified by dividing the total number of ileocolectomy procedures by the time between IBD diagnosis and the patient's last clinic visit, the rationale being that more severe disease would be associated with a more frequent need for surgery. Genotyping for the 83 single-nucleotide polymorphisms associated with IBD was done on a customized Illumina Veracode genotyping platform. Three genetic models (general, additive, and dominant) were used to statistically quantify the genetic association of the studied single-nucleotide polymorphisms to the frequency of surgery after adjusting for covariates (age, smoking, family history, disease location, and disease behavior). RESULTS For the entire group the average number of ileocolectomies per patient was 1.7 (range, 1-5) with an average duration of disease of 14.7 years. Single-nucleotide polymorphism rs4958847 in the IRGM gene (immunity-related GTPase family, M) was the most significant single-nucleotide polymorphism in all 3 models tested (p = 0.007) as being associated with ileocolectomy, and it remained significant even after a Benjamini-Hochberg false-discovery correction for multiple observations. Patients carrying the "at-risk" allele for this single-nucleotide polymorphism (n = 20) had an average of 1 surgery every 6.87 ± 1.33 years in comparison with patients carrying the wild-type genotype (n = 46) who averaged 1 surgery in 11.43 ± 1.21 years (p = 0.007, Mann-Whitney U test). CONCLUSIONS : Single-nucleotide polymorphism rs4958847 in the IRGM gene correlated very significantly with frequency of surgery in patients with ileocolonic Crohn's disease. IRGM is a mediator of innate immune responses and is involved in autophagy. The presence of this IRGM SNP may be a marker for disease severity and/or early recurrence after ileocolectomy and may assist in surgical and medical decision making.
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Affiliation(s)
- Rishabh Sehgal
- Division of Colon and Rectal Surgery, Penn State Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA.
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Bi X, Walsh A, Mahadevan-Jansen A, Herline A. Development of spectral markers for the discrimination of ulcerative colitis and Crohn's disease using Raman spectroscopy. Dis Colon Rectum 2011; 54:48-53. [PMID: 21160313 DOI: 10.1007/dcr.0b013e3181fcf68d] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Ulcerative colitis and Crohn's disease are 2 distinct forms of IBD that can overlap radiologically, endoscopically, and pathologically. This difficulty complicates surgical options. The development of new technologies providing accurate diagnosis of IBD is needed. Raman spectroscopy is a noninvasive method that uses the intrinsic properties of tissue and that tissue's vibrational energy in reaction to light. PURPOSE We hypothesize that Raman spectroscopy can detect the structural and compositional changes that occur in the tissue during the development of inflammatory bowel disease, and thus may offer increased diagnostic certainty in the differentiation between Crohn's disease and ulcerative colitis. METHODS Fresh frozen colon tissue biopsies from patients with ulcerative colitis (n = 12) and with Crohn's disease (n = 9) were measured in vitro using a custom-designed Raman fiber-optic probe. For spectra collection, the probe was placed in gentle contact with the mucosa surface for 3 seconds, with excitation power at 150 mW. Five spectra were acquired from each biopsy to increase the signal-to-noise ratio and to ensure repeatability of data collection. Mean spectra were analyzed for peak difference and molecular origin. RESULTS Significant difference was observed between the spectra from each disease in the spectral regions assigned to nucleic acid, phenylalanine, and lipids. Tissue samples from patients with ulcerative colitis demonstrated higher content of lipid and lower amount of phenylalanine and nucleic acid. These characteristic Raman features could serve as spectral markers that can potentially be applied to distinguish ulcerative colitis and Crohn's disease. CONCLUSIONS This study presents the only application of Raman spectroscopy in the diagnosis of inflammatory bowel disease. The feasibility of this technique in differentially detecting molecular alterations in ulcerative colitis and Crohn's disease has been demonstrated, indicating the potential to improve diagnostic accuracy of inflammatory bowel disease.
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Affiliation(s)
- Xiaohong Bi
- Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA.
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Abstract
PURPOSE Pouchitis and Crohn's-like complications can plague patients after IPAA. NOD2 is an intracellular sensor for bacterial cell wall peptidoglycan. NOD2 mutations compromise host response to enteric bacteria and are increased in Crohn's disease. We hypothesize that IPAA patients with complications (Crohn's disease-like/pouchitis) have a higher rate of NOD2 mutations compared with asymptomatic IPAA patients. METHODS Patients were retrospectively subclassified into the following groups: 1) IPAA with Crohn's-like complications (n = 28, perianal fistula, pouch inlet stricture/upstream small-bowel disease, or biopsies showing granulomata) occurring at least 6 months after ileostomy closure; 2) IPAA with mild pouchitis (n = 33, ≤3 episodes/y for 2 consecutive years); 3) IPAA with severe pouchitis (n = 9, ≥4 episodes/y for 2 consecutive years or need for continuous antibiotics); 4) IPAA without complications or pouchitis (n = 37); 5) patients with Crohn's disease with colitis undergoing total proctocolectomy/ileostomy (n = 11); and 6) healthy controls (n = 269). The 3 NOD2 single-nucleotide polymorphism mutations (rs2066844, rs2066845, and rs2066847) previously identified as associated with Crohn's disease were genotyped using polymerase chain reaction. Groups were compared by use of χ with Yates continuity correction. RESULTS NOD2 mutations were found in 8.5% of healthy controls. NOD2 mutations were significantly higher in the severe pouchitis group (67%) compared with both asymptomatic IPAA (5.4%, P < .001) and IPAA with Crohn's disease-like complications (14.3%, P = .008) groups. CONCLUSIONS 1) Asymptomatic IPAA patients have a low incidence of NOD2 mutations not significantly different from patients with mild pouchitis or healthy controls. 2) Patients with severe pouchitis had the highest incidence of NOD2 mutations, suggesting that this group may have a compromised host defense mechanism to enteric bacteria. 3) Patients with Crohn's-like complications after IPAA have a significantly lower incidence of NOD2 mutations than patients with severe pouchitis, suggesting a different genetic makeup in these 2 patient groups. Preoperative assessment of NOD2 in the equivocal IPAA candidate may predict severe pouchitis and might assist in preoperative surgical decision making.
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Abstract
Inflammatory bowel disease (IBD) is characterized by increasing morbidity and, if suboptimally treated, poor prognosis. Recent evidence strongly suggests that dysfunctional immune responses play an important role in the pathogenesis of IBD. Therefore, immunologically downregulating the overactivated innate and adaptive immune responses may be a better approach to treat IBD than currently used pharmaceutical therapies. In recent years, many new biological therapies have been developed. These therapies are shown to be effective for inducing remission, preventing complications, improving life quality of the patients, and reducing hospitalization and surgical rates. This article introduces and discusses these new biological agents that have been used effectively in clinic for IBD patients.
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Affiliation(s)
- Aiping Bai
- University of Manitoba, Winnipeg, Canada
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Barnett M, Bermingham E, McNabb W, Bassett S, Armstrong K, Rounce J, Roy N. Investigating micronutrients and epigenetic mechanisms in relation to inflammatory bowel disease. Mutat Res 2010; 690:71-80. [PMID: 20188748 DOI: 10.1016/j.mrfmmm.2010.02.006] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2009] [Revised: 01/26/2010] [Accepted: 02/19/2010] [Indexed: 05/28/2023]
Abstract
Epigenomic regulation, via DNA methylation, histone modification and non-coding RNA, is increasingly recognised as having a key role in normal development and function of an organism, acting to control cellular and tissue growth and differentiation. It is also thought to be involved in many complex diseases now common in the Western world, including cardiovascular disease, type 2 diabetes, obesity and inflammatory bowel disease (IBD). There is a range of evidence to suggest that nutrition plays a vital role in the protection from such diseases. However, there is little information about the role of nutrition on the epigenetic regulation of IBD. This review aims to elucidate the interactions of nutrients and the epigenome in IBD. More specifically, the plasticity of epigenetic modifications that occur due to low selenium and folate levels in the diet during gestation and lactation will be discussed. A better understanding of this plasticity, and of nutrient-epigenome interactions, will have important implications for enhancing human health through foods.
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Affiliation(s)
- Matthew Barnett
- Food, Metabolism & Microbiology Section, AgResearch Grasslands, Tennent Drive, Palmerston North 4474, New Zealand.
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Triantafillidis JK, Nadia EF, Fostira F, Terzoudi G, Fouskas J, Pinis S. Turner's syndrome, autoimmune thyroiditis, and Crohn's disease in the same patient: a combination emphasizing the role of X-chromosome in inflammatory bowel disease patients. Inflamm Bowel Dis 2010; 16:1088-9. [PMID: 19821507 DOI: 10.1002/ibd.21125] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
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Michel P, St-Onge L, Lowe AM, Bigras-Poulin M, Brassard P. Geographical variation of Crohn's disease residual incidence in the Province of Quebec, Canada. Int J Health Geogr 2010; 9:22. [PMID: 20462422 PMCID: PMC2877008 DOI: 10.1186/1476-072x-9-22] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2009] [Accepted: 05/12/2010] [Indexed: 12/12/2022] Open
Abstract
Background Crohn's disease (CD) is clinically expressed as a chronic affection of the gastrointestinal tract currently known to have a multifactorial etiology involving a complex pathophysiological host response modulated by genetic susceptibilities, demographic determinants and environmental factors. With more than 20 cases per 100,000 person-years, the province of Quebec, Canada is among regions of the world with highest reported occurrence of CD in relation to other places where comparable estimates are available. This ecological study was designed to provide a medium-scale spatial exploration of CD incidence after accounting for the influence of known population and regional determinants. Health records of consulting patients in southern Quebec were compiled from 1995 to 2000 and used to estimate age and sex standardized rates per health area (n = 156). Various statistical models taking into account the regional effect of Jewish ethnicity, aboriginal ancestry, material deprivation, prescription for oral contraceptives, reportable enteric infection incidence, smoking as well as latitude and longitude locations were fitted. Results The final regression model presented a coefficient of determination of 22.8% and there was evidence of an eastern trend in the residual incidence (p = 0.018). Overall, the smoothed residual incidence presented a heterogeneous spatial pattern with evidence of patches (multiple health areas) of high, low and contrasting values. Health areas with most extreme incidence residuals where also distributed over the whole province including one area in the metropolitan area of Montreal and others in surrounding areas. Conclusions These findings suggest that known populational and regional factors derived through census information only explain a limited fraction of the geographical variation of CD incidence and lead to speculate that the effects of these factors may be incompletely captured (imperfect construction of proxy variables) or that other important factors remain unmeasured. In this view, markers of genetic profiles of homogeneous sub-populations, and other factors linked to agroenvironmental microbial exposure should be further investigated. Once accounting for known factors, it would also be worth comparing adjacent geographical areas demonstrating abrupt changes in residual incidence rates to further explore effect linked to regional factors from those resulting from various reporting systems.
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Affiliation(s)
- Pascal Michel
- Laboratory for Foodborne Zoonoses, Public Health Agency of Canada, Saint-Hyacinthe, Quebec, Canada.
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Cerquetella M, Spaterna A, Laus F, Tesei B, Rossi G, Antonelli E, Villanacci V, Bassotti G. Inflammatory bowel disease in the dog: Differences and similarities with humans. World J Gastroenterol 2010; 16:1050-6. [PMID: 20205273 PMCID: PMC2835779 DOI: 10.3748/wjg.v16.i9.1050] [Citation(s) in RCA: 92] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBD) represent important chronic conditions affecting the gastrointestinal tract in man. However, similar disorders are found in several animal species and the IBD affecting dogs are particularly important. These are encompassed by an umbrella of probably several different entities with common symptoms, some of which seem to share striking similarities with human conditions. This review will focus on the actual knowledge of IBD in dogs, and attempt to identify differences and similarities with human IBD conditions.
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Garrett WS, Glimcher LH. T-bet-/- RAG2-/- ulcerative colitis: the role of T-bet as a peacekeeper of host-commensal relationships. Cytokine 2009; 48:144-7. [PMID: 19666230 DOI: 10.1016/j.cyto.2009.07.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2009] [Accepted: 07/06/2009] [Indexed: 12/13/2022]
Abstract
Inflammatory bowel disease is a disease that reflects a disequilibrium in host-commensal homeostasis. T-bet-/-xRAG2-/- deficient mice develop a spontaneous juvenile ulcerative colitis resulting from a pro-inflammatory response to the commensal microbiota that is dendritic cell and TNF-alpha driven [schematized in Fig. 1]. The TRUC (T-bet-/- RAG2-/- ulcerative colitis) model is discussed in the broader context of the adaptive and innate immune mechanisms that regulate host-commensal relationships within the intestine.
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Affiliation(s)
- Wendy S Garrett
- Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
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