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Single-nucleotide polymorphism at CYP27B1-1260, but not VDR Taq I, is possibly associated with persistent hepatitis B virus infection.

ABSTRACT: Vitamin D, beyond its role in calcium and bone metabolism, exhibits immunomodulatory effects on innate and adaptive immune pathways and is suggestively related to liver diseases.This study investigated the association of single-nucleotide polymorphisms in genes involved in vitamin D functions with hepatitis B virus (HBV) infection.Five hundred Chinese Han subjects, including 274 chronic HBV patients, 68 HBV infection resolvers, and 158 healthy controls without HBV infection, were studied. The CYP27B1-1260 promoter and the VDR Taq I polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism.Although there was no difference between HBV patients and healthy controls, HBV patients and healthy controls had a higher frequency of the CYP27B1-1260 genotype CC (15.0% vs. 2.9%, p=0.004 and 13.3% vs. 2.9%, p=0.006, respectively) and allele C (38.3% vs. 25.7%, p=0.006 and 39.2% vs. 25.7%, p=0.006, respectively) compared with resolvers. The genotype and allele frequencies of the VDR Taq I polymorphism had no difference between patients, resolvers, and healthy controls.These results suggest that the CYP27B1-1260 promoter polymorphism is possibly associated with the persistence, but not susceptibility to HBV infection in Chinese HBV patients, and that the VDR Taq I polymorphism is not suggested to be related to chronic HBV infection.

SUBMITTER: Zhu Q

PROVIDER: S-EPMC3438824 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Single-nucleotide polymorphism at CYP27B1-1260, but not VDR Taq I, is possibly associated with persistent hepatitis B virus infection.

Zhu Qianqian Q Li Na N Han Qunying Q Li Zhu Z Zhang Guoyu G Li Fang F Zhang Pingping P Chen Jinghong J Lv Yi Y Liu Zhengwen Z

Genetic testing and molecular biomarkers 20120901 9

<h4>Background</h4>Vitamin D, beyond its role in calcium and bone metabolism, exhibits immunomodulatory effects on innate and adaptive immune pathways and is suggestively related to liver diseases.<h4>Objective</h4>This study investigated the association of single-nucleotide polymorphisms in genes involved in vitamin D functions with hepatitis B virus (HBV) infection.<h4>Methods</h4>Five hundred Chinese Han subjects, including 274 chronic HBV patients, 68 HBV infection resolvers, and 158 healthy ...[more]

PMID: 22963605

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Project description:BackgroundRecent studies have indicated that abnormal glucose levels and diabetes are negatively associated with the prognosis of patients with chronic hepatitis C virus (HCV) infection. The genetic polymorphism of the promoter region -1260 of a gene encoding the enzyme 1-alpha-hydroxylase (CYP27B1-1260) has been shown to have an impact on the signaling pathways involved in insulin secretion.ObjectivesThe aim is to investigate the effect of CYP27B1-1260 polymorphism on the fasting plasma glucose (FPG) levels in patients with chronic HCV undergoing antiviral therapy.Patients and methodsA total of 461 patients with chronic HCV infection and 300 volunteers without HCV infection were enrolled in an observational cohort study in the China-Japan Union hospital of Jilin University and the Second Hospital of Daqing, Changchun, Jilin Province. Both groups were further divided into normal and abnormal FPG subgroups. The frequencies of the three CYP27B1-1260 genotypes (AA, AC, and CC) were determined in each subgroup. FPG levels were monitored at baseline in HCV and control participants, and both during and after antiviral therapy in HCV infected patients. The frequency of each genotype was determined. Logistic regression analysis was performed to evaluate the risk factors associated with abnormal FPG levels in HCV infected patients undergoing antiviral therapy.ResultsIn HCV infected patients with abnormal FPG levels, the frequency of the genotype CC was significantly higher than that in patients with normal FPG levels (19% vs. 7%, P < 0.001). In contrast, in the control participants, the CC genotype was not significantly different between FPG groups. At baseline, the CC genotype was associate with four times more risk of IFG after adjusting for multiple variables (OR: 4.11; 95%CI: 1.98 - 8.52, P = 0.0001). During 24 weeks of anti-HCV treatment, 38 HCV participants developed newly-diagnosed impaired fasting glucose. The CC genotype markedly increased the risk for newly developed IFG (OR: 26.54; 95%CI: 7.80 - 90.32, P < 0.0001). Other risk factors included age and body mass index.ConclusionsCYP27B1-1260 polymorphism is associated with abnormal glucose metabolism in HCV infected patients. HCV infected individuals with CYP27B1-1260 genotype CC appeared to have an increased risk of developing abnormal FPG levels.

Project description:AIM:To evaluate the association of IFNL3 (IL28B) SNP rs4803217 with severity of disease and treatment outcome in chronic hepatitis C (CHC). METHODS:The study enrolled 196 CHC Polish patients (82 women and 114 men in age 20-64) infected with hepatitis C virus (HCV) genotype 1. They were treatment naïve and qualified to pegylated interferon alpha (PEG-IFN-?) and ribavirin (RBV) therapy. The analyzed baseline parameters included: degree of inflammation, stage of fibrosis, viral load as well as alanine aminotransferase (ALT), asparagine aminotransferase (AST) and total bilirubin (TBIL). The analysis of response to therapy included: sustained virological response (SVR), defined as undetectable serum HCV RNA level six month after completion of 48-wk therapy, and relapse, defined as achieving undetectable viral load at the end of treatment but not SVR. HCV genotyping and HCV RNA quantification were performed using commercially available tests. DNA was isolated from peripheral blood mononuclear cells or from buccal cell swabs. In addition to rs4803217, also single nucleotide polymorphisms (SNPs) (rs12979860, rs8099917 and rs12980275) of known significance in predicting of HCV clearance were analyzed. SNPs were determined by high resolution melt analysis and confirmed by sequencing of amplicons. RESULTS:Frequency of rs4803217 genotypes in studied group was as follows: 27.55%; 54.59% and 17.86% for CC, CA and AA, respectively. The rs4803217 SNP, similar to other analyzed SNPs, was not associated with severity of CHC (grade of inflammation, stage of fibrosis, baseline viral load as well as biochemical parameters: ALT, AST, TBIL). It was demonstrated that the rs4803217C allele is associated with SVR (C vs A: P < 0.0001; dose of C allele: P = 0.0002) and non-relapse (C vs A: P = 0.001; dose of C allele: P = 0.002). Moreover, it was found that patients with CC genotype have significantly higher response rates as compared with CA/AA patients (P < 0.0001), whereas patients carrying A allele are significantly predisposed to relapse after treatment (P = 0.0007). Moreover, the association of rs4803217 with SVR was comparable to that of rs12979860 and stronger as observed for rs12980275 and rs8099917. Association of rs4803217 with relapse, was the strongest as compared with the other SNPs. The analysis of combined rs4803217 and rs8099917 genotypes demonstrated that additional genotyping of rs8099917 had no significant impact on the prediction of SVR. Multivariate analysis revealed that among analyzed SNPs only rs4803217 is an independent predictor of SVR (P = 0.016) and relapse (P = 0.024). CONCLUSION:The rs4803217 SNP is a strong, independent and superior predictor of SVR and relapse in HCV genotype 1 infected CHC patients treated with PEG-IFN-? and RBV.

Dataset Information

Single-nucleotide polymorphism at CYP27B1-1260, but not VDR Taq I, is possibly associated with persistent hepatitis B virus infection.

Publications

Single-nucleotide polymorphism at CYP27B1-1260, but not VDR Taq I, is possibly associated with persistent hepatitis B virus infection.

Similar Datasets

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