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JAK1 gene polymorphisms are associated with the outcomes of hepatitis B virus infection, but not with ? interferon therapy response in a Han Chinese population.

ABSTRACT: Janus kinase 1 (JAK1) is a key member in the interferon (IFN) signaling pathway. Recent studies suggested single-nucleotide polymorphisms (SNPs) in IFN pathway genes are associated with outcomes of hepatitis B virus (HBV) infection and response to IFN? therapy. The aim of the study is to investigate whether SNPs in JAK1 were associated with outcomes of HBV infection and response to IFN? therapy.We enrolled 395 chronic hepatitis B (CHB) patients and 251 subjects with the inactive carrier state, and 256 CHB patients who received IFN? treatment, with therapy efficacy evaluated. Twelve SNPs: rs310227, rs7531799, rs7546545, rs17127174, rs3790541, rs10493373, rs2780898, rs310247, rs310196, rs2780895, rs4244165, and rs17127024 in JAK1, which could represent all SNPs with minor allele frequency >0.2 recorded in the HapMap database were genotyped using a polymerase chain reaction-restriction fragment length polymorphism protocol and the TaqMan method.SNP rs17127024 was associated with outcomes of HBV infection in an allele frequency (p=0.014) and genotype distributions (p=0.031), while SNP rs4244165 was associated with outcomes of HBV infection only in genotype distributions (p=0.008). There were no significant differences in allele frequencies and genotype distributions of these SNPs between the response group and the nonresponse group to IFN? therapy.SNPs rs4244165 and rs17127024 in JAK1 were associated with outcomes of HBV infection, but not with response to IFN? therapy.

SUBMITTER: Chen K

PROVIDER: S-EPMC3468121 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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JAK1 gene polymorphisms are associated with the outcomes of hepatitis B virus infection, but not with α interferon therapy response in a Han Chinese population.

Chen Kangmei K Min Hanyi H Wu Xiaopan X Zhu Xilin X Li Zhuo Z Li Hui H Liu Ying Y

Genetic testing and molecular biomarkers 20120817 10

<h4>Aims</h4>Janus kinase 1 (JAK1) is a key member in the interferon (IFN) signaling pathway. Recent studies suggested single-nucleotide polymorphisms (SNPs) in IFN pathway genes are associated with outcomes of hepatitis B virus (HBV) infection and response to IFNα therapy. The aim of the study is to investigate whether SNPs in JAK1 were associated with outcomes of HBV infection and response to IFNα therapy.<h4>Methods</h4>We enrolled 395 chronic hepatitis B (CHB) patients and 251 subjects with ...[more]

PMID: 22901011

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Project description:AimTo investigate the association between interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) polymorphisms and interferon-α (IFNα) treatment efficiency among Chinese hepatitis B virus (HBV) infection patients.MethodsTwo hundred and twenty five newly diagnosed chronic hepatitis B (CHB) patients were enrolled in the study. All of these patients received IFNα treatment for a course of 48 wk, and were followed up for 24 wk after the treatment was end. Clinical information about virological response, hepatitis B e antigen (HBeAg) seroconversion rate and combined response at the end of the treatment, as well as the sustained response by the time of following up 24 wk after the treatment, was collected. Four tag-single nucleotide polymorphisms (SNPs) of IFIT1 were selected and assessed for their association with these clinical outcomes.ResultsAt the end of the treatment, HBeAg seroconversion was observed in 27.1% patients. Thirty-six point nine percent patients achieved virological response, and 15.6% patients exhibited combined response. Sustained response was obtained in 26.2% patients. The main HBV genotype of the study was genotype B. Patients who infected with HBV genotype B or C showed better treatment efficiency, no matter which clinical outcome was considered. Among the four SNPs assessed, rs303218 (A > G) was found to be significantly associated with the end point virological response when assuming additive model [OR = 0.64 (95%CI: 0.42-0.96), P = 0.032]. Patients who carried rs303218 GG genotype had a rather higher rate of achieving virological response (response rate: 52%, OR = 0.40, 95%CI: 0.18-0.91; P = 0.028) when compared to those had AA genotype (response rate: 27%). The most significant interaction was observed in patients who had relative lower baseline aspartate transaminase. No association between SNPs and HBeAg seroconversion, combined response or sustained response was observed.ConclusionIFIT1 involves in the regulation of IFNα treatment for CHB and its polymorphism rs303218 can predict the end point virological response. The finding requires further validation.

Dataset Information

JAK1 gene polymorphisms are associated with the outcomes of hepatitis B virus infection, but not with ? interferon therapy response in a Han Chinese population.

Publications

JAK1 gene polymorphisms are associated with the outcomes of hepatitis B virus infection, but not with α interferon therapy response in a Han Chinese population.

Similar Datasets

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