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HBV Viral Load and Liver Enzyme Levels May Be Associated with the Wild MBL2 AA Genotype. Mediators Inflamm 2017; 2017:3718451. [PMID: 28408790 PMCID: PMC5376955 DOI: 10.1155/2017/3718451] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Revised: 01/24/2017] [Accepted: 02/06/2017] [Indexed: 01/26/2023] Open
Abstract
The present study investigated the frequencies of rs1800450 (MBL ⁎B, G>A), rs1800451 (MBL ⁎C, G>A), and rs5030737 (MBL ⁎D, C>T) polymorphisms in exon 1 of the MBL2 gene among patients with chronic viral hepatitis. Blood samples from patients infected with hepatitis B virus (HBV; n = 65), hepatitis C virus (HCV; n = 92), and a noninfected control group (n = 300) were investigated. The presence of polymorphisms was detected using a real-time polymerase chain reaction to correlate with liver disease pathogenesis and fibrosis staging according to the Metavir classification. The genotypic and allelic frequencies showed no significant differences between the groups, but patients with active HBV and the wild AA genotype presented a positive correlation between increased transaminase and HBV DNA levels and the presence of mild to moderate fibrosis. Patients with HCV and the wild AA genotype presented mild inflammation and higher HCV RNA levels, although the same association was not observed for the fibrosis scores. The results suggest that the mutations in exon 1 of the MBL2 gene do not contribute directly to the clinical and laboratory features of HCV and HBV infections, but further studies should be performed to confirm whether the wild AA genotype has indirect effect on disease progression.
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Gu X, Ji Q, Wang H, Jiang M, Yang J, Fang M, Wang M, Gao C. Genetic variants of mannose-binding lectin 2 gene influence progression and prognosis of patients with hepatitis B virus infection in China. Clin Res Hepatol Gastroenterol 2016; 40:614-621. [PMID: 26857650 DOI: 10.1016/j.clinre.2015.12.015] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2015] [Accepted: 12/21/2015] [Indexed: 02/04/2023]
Abstract
AIM Mannose-binding lectin (MBL) is a member of the calcium-dependent collectin family involved in the innate immune system that mediates phagocytosis and activates complement by binding to carbohydrate motifs. We studied allele and haplotype frequencies of -221C/G and codon 54G/A in MBL2 gene to reveal their relationship with the developing and progression of hepatitis B virus (HBV)-related liver diseases. METHODS This study was performed in 171 healthy controls, 133 chronic hepatitis B (CHB) patients, 97 patients with HBV-related liver cirrhosis (LC) and 334 HBV-related hepatocellular carcinoma (HCC) patients. The genotypes of these two polymorphisms in these subjects were detected using polymerase chain reaction-ligation detection reaction (PCR-LDR) method. Stratification analyses by clinical characteristics and survival analysis of HCC patients were also performed according to their genotypes. RESULTS The genotype and allele frequencies at codon 54 manifested a significant difference between healthy controls and patients with progressive HBV-related liver diseases, especially liver cirrhosis. Allele A appeared to have protective effect from developing LC and HCC compared with G allele. The percentages of the patients with G allele at -221C/G increased in HBV-related disease groups. When combined together as a haplotype, lower haplotype AC frequency was associated with a decreased risk for the progression of HBV-related liver diseases and HCC developing. Furthermore, HCC patients with G allele at codon 54 showed to have better survival than those with A allele. CONCLUSION These results indicated that polymorphisms in MBL2 gene may influence susceptibility, progression and prognosis of HBV-related liver diseases.
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Affiliation(s)
- Xing Gu
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai 200438, PR China
| | - Qiang Ji
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai 200438, PR China
| | - Hao Wang
- Department of Laboratory Medicine, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, PR China
| | - Mingming Jiang
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai 200438, PR China
| | - Juan Yang
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai 200438, PR China
| | - Meng Fang
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai 200438, PR China
| | - Mengmeng Wang
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai 200438, PR China
| | - Chunfang Gao
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai 200438, PR China.
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Abstract
Persistent hepatitis B virus (HBV) infection is a significant public health problem because it is a major cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). Roughly one-third of the world population has been infected with HBV and there are about 350 million (5%-6%) persistent carriers. HBV causes 80% of all liver cancer cases and is the second most important carcinogen, after smoking tobacco. There is an approximate 90% risk of becoming a persistent carrier following perinatal infection in infants born to e antigen positive carrier mothers and a 30% risk in pre-school children. Only 5%-10% of adults become persistent carriers following infection. Of individuals persistently infected with HBV, 10%-30% will develop liver cirrhosis and HCC. These highly variable outcomes in both clearance rates and disease outcomes in persistently infected individuals cannot be fully explained by differences in immunological, viral or environmental factors. Thus, differences in host genetic factors may affect the natural history of hepatitis B.
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Association between Mannose-binding lectin gene polymorphisms and hepatitis B virus infection: a meta-analysis. PLoS One 2013; 8:e75371. [PMID: 24116040 PMCID: PMC3792921 DOI: 10.1371/journal.pone.0075371] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2013] [Accepted: 08/11/2013] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVE The results of studies on the relation between Mannose-binding lectin gene (mbl2) polymorphism and HBV infection were contradictory and inconclusive. In order to shed a light on these inconsistent findings and to clarify the role of mbl2 polymorphisms in susceptibility or progression of chronic hepatitis B (CHB), a meta-analysis was performed. METHODS PubMed and Embase were searched for available articles. A meta-analysis was performed to examine the association between mbl2 polymorphisms and chronicity or progression of hepatitis B infection. Odds ratio (OR) and its 95% confidence interval (CI) served as indexes. RESULTS A total of 17 eligible studies were involved, including 2151 healthy controls (HC), 1293 spontaneous recovered (SR) patients with acute infection, 2337 cases with chronic hepatitis B (CHB) and 554 cases with progressive hepatitis B. There was no evidence of significant association between mbl2 exon1 polymorphisms and CHB risk in any genetic model or pairwise comparisons when compared with HC group or SR group. In the stratified analysis of ethnic groups, also no obvious relation between mbl2 polymorphism and CHB risk was identified. There was still no significant association between the complete mbl2 genotypic profile (including both the exon1 and the promoter gene) polymorphisms and CHB risk, as compared with SR group. However, it was found that there was an association between the mbl2 AO/OO genotype and severe hepatitis B (SHB) or liver cirrhosis (LC) (LC vs. HC:OR=3.66, 95%CI, 2.38-5.63; SHB vs. HC, OR=3.88, 95%CI, 2.26-6.64), but there was no relationship between the mbl2 AO/OO genotype and hepatocellular carcinoma (HCC) (OR=1.26, 95%CI, 0.82-1.94). CONCLUSION The present meta-analysis indicated that mbl2 exon1 polymorphisms might not significantly associate with chronicity of HBV infection, but might be significantly related to the progressive HBV such as SHB and LC.
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Abstract
BACKGROUND Tuberculosis (TB) has recently re-emerged as a major public health threat worldwide. There is strong evidence that host genetic factors influence individual susceptibility to TB and that, once infected, young children and immunocompromised patients are at increased risk for mycobacterial disease and progression to extrapulmonary lymphadenitis. METHODS The association between polymorphisms of mannose-binding lectin and the susceptibility of 139 children with cervical mycobacterial lymphadenitis and infected with Mycobacterium tuberculosis was investigated. RESULTS The frequencies of genotypes A/B and B/B, based on codon 54 polymorphisms, were significantly different in TB-infected versus healthy control subjects. The frequency of the A/B genotype was significantly lower in TB-infected children (odds ratio = 0.56; 95% confidence interval: 0.36-0.87; P = 0.01), and the B/B genotype was significantly higher in TB-infected children (odds ratio = 4.68; 95% confidence interval: 1.35-16.3; P = 0.01) compared with healthy controls. The HYB haplotype appeared significantly more often to be protective in the healthy control population (odds ratio = 0.23; 95% confidence interval: 0.05-0.96; P = 0.046). Ex vitro phagocytosis assays indicated that high-expression mannose-binding lectin genotypes are associated with an increased risk of infection with M. tuberculosis. CONCLUSIONS The present study suggests that mannose-binding lectin can protect against TB or predispose the host to the disease depending on the haplotype pair of the host. The low-expression genotype A/B and the HYB haplotype may be associated with protection against intracellular mycobacterial infections, whereas the high-expression genotype A/A may confer susceptibility to disease.
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Filho RM, Carmo RF, Catsman C, Souza C, Silva A, Moura P, Tenorio AL, Vasconcelos LRS, Cavalcanti MDSM, Pereira LMMB. High frequency of variant alleles of the mannose-binding lectin 2 (MBL2) gene are associated with patients infected by hepatitis B virus. Viral Immunol 2011; 23:449-53. [PMID: 20712490 DOI: 10.1089/vim.2009.0105] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Patients with hepatitis B virus (HBV) infection may develop severe chronic liver disease. Carriers of HBV have an increased risk of developing cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Worldwide an estimated 350 million people are infected with HBV, and 15-40% will develop serious sequelae in their lifetime. In our study we investigated the association of single nucleotide polymorphisms (SNPs) in the first exon and promoter region of the mannose-binding lectin gene 2 (MBL2) situated on chromosome 10, with susceptibility to HBV infection. One-hundred and two patients infected with HBV were included in this study, and 232 uninfected individuals were used as healthy controls. Genotyping of the first exon (alleles A/O) was performed using a melting temperature assay. Genotyping of the promoter region (-550 H/L; -221 Y/X) was performed using the Taqman PCR technique. In the HBV-infected group we found a significantly increased frequency of haplotypes associated with low serum MBL. Our findings may indicate that MBL has a protective role against HBV infection in the studied population.
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Engin A, Ugurlu S, Caglar E, Oztop AY, Inan D, Elaldi N, Dokmetas I, Bakir M. Serum Levels of Mannan-Binding Lectin in Patients with Crimean-Congo Hemorrhagic Fever. Vector Borne Zoonotic Dis 2010; 10:1037-41. [DOI: 10.1089/vbz.2009.0060] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Aynur Engin
- Department of Infectious Diseases and Clinical Microbiology, Cumhuriyet University School of Medicine, Sivas, Turkey
| | - Serdal Ugurlu
- Department of Internal Medicine, Cumhuriyet University School of Medicine, Sivas, Turkey
| | - Erkan Caglar
- Department of Internal Medicine, Istanbul University Cerrahpasa School of Medicine, Istanbul, Turkey
| | - Atifet Yasemin Oztop
- Department of Microbiology and Clinical Microbiology, Cumhuriyet University School of Medicine, Sivas, Turkey
| | - Dursun Inan
- Department of Internal Medicine, Cumhuriyet University School of Medicine, Sivas, Turkey
| | - Nazif Elaldi
- Department of Infectious Diseases and Clinical Microbiology, Cumhuriyet University School of Medicine, Sivas, Turkey
| | - Ilyas Dokmetas
- Department of Infectious Diseases and Clinical Microbiology, Cumhuriyet University School of Medicine, Sivas, Turkey
| | - Mehmet Bakir
- Department of Infectious Diseases and Clinical Microbiology, Cumhuriyet University School of Medicine, Sivas, Turkey
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Cheong JY, Cho SW, Oh B, Kimm K, Lee KM, Shin SJ, Lee JA, Park BL, Cheong HS, Shin HD, Cho BY, Kim JH. Association of interleukin-18 gene polymorphisms with hepatitis B virus clearance. Dig Dis Sci 2010; 55:1113-9. [PMID: 19466545 DOI: 10.1007/s10620-009-0819-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2009] [Accepted: 04/12/2009] [Indexed: 01/12/2023]
Abstract
The outcome of hepatitis B virus (HBV) infection can be affected by host immune factors. Interleukin-18 (IL-18) was originally discovered as an interferon-gamma-inducing factor and plays a critical role in immune response. We assessed the association between the clearance of HBV infection and single-nucleotide polymorphisms (SNPs) in the IL-18 gene. Between March 2002 and December 2004, a total of 1,050 Korean subjects were enrolled in the study and divided into two groups: (1) the HBV spontaneous recovery group (n = 320) and (2) the chronic HBV carrier group (n = 730). We analyzed SNPs at four polymorphic sites in the IL-18 gene at positions -667G>T, -148G>C, +8925C>G, and +13925A>C. We observed that the subjects bearing the IL-18 -148C allele [odds ratio (OR), 0.25; confidence interval (CI), 0.09-0.68; P = 0.01], the +8925G allele (OR, 0.36; CI, 0.15-0.88; P = 0.02), and the +13925C allele (OR, 0.25; CI, 0.13-0.82; P = 0.01) were significantly associated with HBV clearance in a recessive model. This study indicates that the -148C, +8925G, and +13925C alleles of the IL-18 gene are likely associated with HBV clearance in a Korean population.
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Affiliation(s)
- Jae Youn Cheong
- Department of Gastroenterology, Genomic Research Center for Gastroenterology, Ajou University School of Medicine, San-5 Wonchon-Dong, Youngtong-ku, Suwon, 442-721, South Korea
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Fletcher GJ, Gnanamony M, Samuel P, Ismail AM, Kannangai R, Daniel D, Eapen CE, Abraham P. Association of mannose-binding lectin polymorphisms and HBV outcome in a South Indian population. Int J Immunogenet 2010; 37:177-84. [PMID: 20193030 DOI: 10.1111/j.1744-313x.2010.00908.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Mannose binding lectin (MBL) is an important innate immune system pattern recognition molecule. The MBL gene polymorphisms are reported to play a crucial role in outcome of hepatitis B virus (HBV) infection. In this study, we ascertained the association of MBL genotypes with HBV outcome in a South Indian population. The MBL gene polymorphisms at codons 52, 54 and 57 of exon I, and promoter polymorphisms at -221 were typed by polymerase chain reaction-sequence specific primer in spontaneously recovered and in chronic HBV group. The allele frequency of codon 52 'C' was significantly higher in chronic HBV group than in the recovered group (98.5% vs. 93.6%; P = 0.003) and codon 52 'T' was significantly higher in recovered group than in the chronic group (6.4% vs. 1.5%; P = 0.003). In multivariate analysis, after adjusting for age, sex and state of origin, codon 52 'CC' and 'CT' genotypes were significantly associated with chronicity and recovery respectively [odds ratio (OR), 0.25; 95% confidence interval (CI), 0.08-0.80, P = 0.02] in co-dominant analyzing models. This was re-affirmed in analysis performed exclusively on Tamil Nadu subjects (OR, 0.23; 95% CI, 0.06-0.93, P = 0.039). The frequency of low/none haplotype (XY/O) was significantly higher in recovered group than in chronic group (15.6% vs 7.5%) and associated with spontaneous recovery (OR, 2.28; 95% CI, 1.04-4.99, P = 0.035). Our results provide preliminary evidence that inheritance of codon 52 genotypes and XY/O haplotype associated with low MBL level substantially determine the outcome of HBV infection in a sympatrically isolated South Indian population.
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Affiliation(s)
- G J Fletcher
- Department of Gastrointestinal Sciences, Christian Medical College, Vellore, Tamil Nadu, India
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Kim YS, Cheong JY, Cho SW, Lee KM, Hwang JC, Oh B, Kimm K, Lee JA, Park BL, Cheong HS, Shin HD, Kim JH. A functional SNP of the Interleukin-18 gene is associated with the presence of hepatocellular carcinoma in hepatitis B virus-infected patients. Dig Dis Sci 2009; 54:2722-8. [PMID: 19757044 DOI: 10.1007/s10620-009-0970-6] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2009] [Accepted: 08/24/2009] [Indexed: 12/16/2022]
Abstract
BACKGROUND/AIM The natural course of hepatitis B virus (HBV) infection is likely related to host immune factors. Interleukin-18 (IL-18) plays a significant role in immune defense. This study was undertaken to determine the association between the presence of hepatocellular carcinoma (HCC) and single-nucleotide polymorphisms (SNPs) in the IL-18 gene in HBV-infected patients. METHODS Between March 2002 and December 2004, 730 Korean subjects were enrolled in two different groups: (1) chronic carrier without HCC (n=637) and (2) HCC (n=93). We analyzed SNPs at four polymorphic sites in the IL-18 gene at positions -667G>T, -148G>C, +8925C>G, and +13925A>C in the study subjects. To evaluate the functional significance of SNPs in the IL-18 gene promoter region, we performed a reporter gene assay in HepG2 and Hep3B cells transfected with different alleles. RESULTS The IL-18 -148C allele, +8925G allele, +13925C allele, and haplotype 3 (TCGC) were associated with the presence of HCC in codominant and dominant models. Furthermore, functional analyses using the reporter gene assay revealed that the -148C allele conferred significantly lower promoter activity. CONCLUSIONS This study indicates that the -148C, +8925G, and +13925C alleles of the IL-18 gene are associated with the presence of HCC and the 148G>C SNP is functionally important in determining disease outcome.
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Affiliation(s)
- Yong Seok Kim
- Department of Biochemistry and Molecular Biology, Hanyang University College of Medicine, Seoul, South Korea
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Ruseva M, Kolev M, Dagnaes-Hansen F, Hansen SB, Takahashi K, Ezekowitz A, Thiel S, Jensenius JC, Gadjeva M. Mannan-binding lectin deficiency modulates the humoral immune response dependent on the genetic environment. Immunology 2009; 127:279-88. [PMID: 19476514 DOI: 10.1111/j.1365-2567.2008.03016.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Mannan-binding lectin (MBL) is a plasma protein implicated in innate immune defence against a broad range of microorganisms, including viruses. It is also thought that MBL plays a role in the recruitment of the specific clonal immune response. This was studied by injecting soluble hepatitis B surface antigen (HBsAg) intravenously into mice deficient in both MBL-A and MBL-C (MBL DKO mice). The MBL DKO animals on mixed genetic background (SV129EvSv x C57BL/6) produced higher antibody titres than the wild-type littermates. After primary challenge with the antigen the immunoglobulin M anti-HBsAg antibody titres were threefold higher in the MBL DKO mice than in the wild-type mice. Following the boost, the immunoglobulin G anti-HBsAg antibody titres were 10-fold higher in the MBL DKO mice, suggesting that MBL plays a role in a negative feedback regulation of adaptive immunity. However, the modulating effect of MBL was dependent on the genetic environment. The MBL DKO mice backcrossed on a C57BL/6 background showed the opposite response with the MBL DKO mice now producing fewer antibodies than the wild-type animals, whereas MBL deficiency in mice with the SV129EvSv background did not show any effect in antibody production. These findings indicate that the modifying effect of MBL on the humoral immune response is influenced by the genetic environment.
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Affiliation(s)
- Marieta Ruseva
- Department of Medical Microbiology and Immunology, University of Aarhus, Denmark
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Mannose-binding lectin gene polymorphisms are not associated with susceptibility to hepatitis C virus infection in the Brazilian Amazon region. Hum Immunol 2009; 70:754-7. [PMID: 19540295 DOI: 10.1016/j.humimm.2009.06.014] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2009] [Revised: 06/10/2009] [Accepted: 06/15/2009] [Indexed: 11/21/2022]
Abstract
The present study compares the genotype frequencies between two population groups composed by 73 hepatitis C virus (HCV)-infected patients and 92 seronegative controls and investigates the role of allele variants as a possible factor in the susceptibility to HCV infection and the influence on disease progression. The identification of MBL*B and MBL*C alleles was performed by restriction fragment length polymorphism analysis of the 349-bp product using BanI and MboII restriction enzymes, respectively, and a polymerase chain reaction-sequence-specific polymorphism for discrimination of MBL*D. The analysis of allele and genotype frequencies between an HCV-infected group and seronegative controls did not indicate significant differences. The comparison of chronically infected subjects with and without liver cirrhosis was also not statistically significant. The odds ratio estimations were not significant, and the values obtained cannot suggest that the presence of allele variant MBL*B could have some influence in the risk of HCV infection progression to liver cirrhosis and that the presence of allele MBL*D could confer some protection against disease progression, but a larger sample size is necessary to confirm the present results.
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Tsai CC, Lin TM, You HL, Eng HL. Mannose-binding lectin in high-risk human papillomavirus infection. Am J Obstet Gynecol 2009; 200:618.e1-6. [PMID: 19371855 DOI: 10.1016/j.ajog.2009.02.016] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2008] [Revised: 08/28/2008] [Accepted: 02/11/2009] [Indexed: 11/26/2022]
Abstract
OBJECTIVE Mannose-binding lectin (MBL) is a serum lectin that mediates phagocytosis and activates complement. We investigated the association of mbl-2 functional polymorphisms with human papillomavirus (HPV) infection, which is a primary etiologic factor for cervical cancer. STUDY DESIGN The frequencies of haplotypes and genotypes of mbl-2 exon1 and promoter region variants were analyzed in 150 patients with HPV and 277 control subjects with no HPV. Unconditional logistic regression analysis was performed to evaluate an association between specific mbl-2 alleles and susceptibility to HPV infection. RESULTS The frequency of high-producer mbl-2 genotypes was higher in patients with HPV than in control subjects with no HPV (P = .001). The genotype of the mbl-2 gene polymorphisms represented the least significant risk for the group with HPV. CONCLUSION Certain polymorphisms in the MBL promoter region are increased among cervical samples that demonstrate HPV infection. This finding suggests a potential link between MBL and high-risk HPV infection.
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Koutsounaki E, Goulielmos GN, Koulentaki M, Choulaki C, Kouroumalis E, Galanakis E. Mannose-binding lectin MBL2 gene polymorphisms and outcome of hepatitis C virus-infected patients. J Clin Immunol 2008; 28:495-500. [PMID: 18592362 DOI: 10.1007/s10875-008-9201-8] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2008] [Accepted: 03/26/2008] [Indexed: 01/27/2023]
Abstract
INTRODUCTION Mannose-binding lectin (MBL) is involved in host's response to several infections including hepatitis B but little is known about MBL and hepatitis C virus (HCV) infection. The present study attempts to investigate whether MBL2 genotype and serum MBL levels affect the course of HCV infection. RESULTS AND DISCUSSIONS We investigated the variant alleles in MBL2 gene promoter and exon-1 regions in 80 Caucasian HCV-infected patients. Mutations in MBL2 were determined by polymerase chain reaction and restriction fragment length polymorphisms analysis. Serum MBL levels were measured by ELISA. Polymorphism homozygosity in exon-1 region was significantly related to lower serum MBL levels (p < 0.001), to liver inflammation (p = 0.034, OR = 11.7) and, in a lesser degree, to fibrosis. Polymorphisms in promoter sites -221nt and -550nt were not shown to be related with serum MBL levels or progress to liver inflammation and fibrosis. Serum MBL levels were adversely associated with progression to fibrosis (p = 0.037). Response to antiviral treatment was related to hepatitis C virus genotype (p < 0.001, OR = 10.9), but not to MBL2 genotype or serum MBL levels. CONCLUSION These findings suggest that polymorphisms in MBL2 gene exon-1 region are related to low serum MBL levels and progression of HCV infection to liver inflammation and fibrosis.
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Affiliation(s)
- Eirini Koutsounaki
- Laboratory of Internal Medicine, Faculty of Medicine, University of Crete, P.O. Box 2208, Heraklion 710 03, Greece.
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Cheong JY, Cho SW, Lee JA, Lee KJ, Wang HJ, Lee JE, Kim JH. Matrix metalloproteinase-3 genotypes influence recovery from hepatitis B virus infection. J Korean Med Sci 2008; 23:61-5. [PMID: 18303200 PMCID: PMC2526506 DOI: 10.3346/jkms.2008.23.1.61] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
The reasons for the viral persistence of hepatitis B virus (HBV) infection are unknown, but are probably related to host immune factors. Several matrix metalloproteinases (MMPs) can regulate an inflammatory response. The aim of this study was to assess the effects of the single nucleotide polymorphisms (SNPs) of MMP-3 and -9 genes on the susceptibility to persistent HBV infection. We studied 489 Korean patients with HBV infection (144 inactive carriers, 182 chronic hepatitis, and 163 liver cirrhosis) and 174 healthy individuals who had recovered from HBV infection. MMP-3 gene SNPs were identified at two polymorphic sites (codon 45 [E45K] and codon 96 [D96D]) and MMP-9 gene SNPs at three polymorphic sites (codon 279 [R279Q], codon 607 [G607G], and codon 668 [Q668R]) in study subjects. The frequency of T allele at third position of codon 96 in the MMP-3 gene was higher in HBV persistence patients when analyzed by co-dominant model (age- and sex-adjusted OR=1.242, 95% CI= 1.001-1.540, p=0.049). In conclusion the T allele at the third position of codon 96 in the MMP-3 gene might be associated with persistent HBV infection.
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Affiliation(s)
- Jae Youn Cheong
- Department of Gastroenterology, Genomic Research Center for Gastroenterology, Suwon, Korea
| | - Sung Won Cho
- Department of Gastroenterology, Genomic Research Center for Gastroenterology, Suwon, Korea
| | - Jung A Lee
- Department of Gastroenterology, Genomic Research Center for Gastroenterology, Suwon, Korea
| | - Kwang Jae Lee
- Department of Gastroenterology, Genomic Research Center for Gastroenterology, Suwon, Korea
| | - Hee Jung Wang
- Department of General Surgery, Ajou University School of Medicine, Suwon, Korea
| | | | - Jin Hong Kim
- Department of Gastroenterology, Genomic Research Center for Gastroenterology, Suwon, Korea
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Kang M, Wang HW, Cheng PX, Yin ZD, Li XO, Shi H, Hu XF. Lack of association between mannose-binding lectin gene polymorphisms and juvenile idiopathic arthritis in a Han population from the Hubei province of China. Arthritis Res Ther 2007; 8:R85. [PMID: 16681863 PMCID: PMC1779397 DOI: 10.1186/ar1953] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2006] [Revised: 03/02/2006] [Accepted: 04/09/2006] [Indexed: 12/17/2022] Open
Abstract
Many studies have reported that polymorphisms of the mannose-binding lectin (MBL) gene are associated with autoimmune disease. Here, we investigate the relationship between MBL gene polymorphisms and susceptibility to juvenile idiopathic arthritis (JIA) in a Han-nationality population from the Hubei province of China. PCR-restriction fragment length polymorphism was used to investigate polymorphisms of codons 54 and 57 in exon 1 of the MBL gene in 93 patients with JIA and 48 control children. Neither group showed codon 57 polymorphisms. There was no significant difference in the genotypic frequencies of codon 54 between patients with JIA and healthy controls (wild type, 71.0% versus 75.0%, respectively; heterozygous type, 25.8% versus 25.0%, respectively; and homozygous type, 3.2% versus 0.0%, respectively). In addition, no association was found between the subgroups of patients with JIA and control individuals. Our results provide no evidence for a relationship between MBL gene mutation and susceptibility to JIA.
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Affiliation(s)
- Min Kang
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Hua Zhong University of Science and Technology, 1095 Jie Fang Avenue, Wuhan 430030, Hubei Province, China
| | - Hong-Wei Wang
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Hua Zhong University of Science and Technology, 1095 Jie Fang Avenue, Wuhan 430030, Hubei Province, China
| | - Pei-Xuan Cheng
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Hua Zhong University of Science and Technology, 1095 Jie Fang Avenue, Wuhan 430030, Hubei Province, China
| | - Zun-Dong Yin
- Chinese Center for Disease Control and Prevention, 27 Nan Wei Road, Beijing 100050, China
| | - Xiao-Ou Li
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Hua Zhong University of Science and Technology, 1095 Jie Fang Avenue, Wuhan 430030, Hubei Province, China
| | - Hong Shi
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Hua Zhong University of Science and Technology, 1095 Jie Fang Avenue, Wuhan 430030, Hubei Province, China
| | - Xiu-Fen Hu
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Hua Zhong University of Science and Technology, 1095 Jie Fang Avenue, Wuhan 430030, Hubei Province, China
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