The association study of the polymorphisms of interferon-inducible genes OAS and the seroconversion of HBsAg and HBeAg in patients with HBeAg positive chronic hepatitis B infection receiving interferon-αand nucleotide analogue combined therapy
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摘要: 目的探讨HBeAg阳性慢性乙型肝炎(CHB)患者经干扰素(IFN)α为基础的抗病毒治疗血清学转换与2’,5’寡腺苷酸合成酶(OAS)1、2、3及OASL基因单核苷酸多态性(SNP)的关系。方法 277例HBeAg阳性CHB患者给予IFNα及核苷酸类似物(NA)联合抗病毒治疗,依据HBsAg及HBeAg转换与否评价疗效,分为HBsAg转换组、HBeAg转换组及无应答组(NR),同时纳入50例HBV自限性感染者作为对照。应用多聚酶链式反应(PCR)及限制性片段长度多态性(RFLP)检测宿主的抗病毒蛋白OAS1基因内含子区rs2285934(A/C)位点、OAS2基因外显子-2区rs2072138(C/G)位点、OAS3基因外显子-8区rs2072136(C/T)位点及OASL基因内含子区rs11849829(A/G)位点SNP,并分别比较OAS基因单位点、基因型及单体型与疗效的相关性。结果 277例患者中HBsAg转换组41例(14.80%),HBeAg转换组102例(36.82%),NR组134例(48.38%)。OAS3等位基因C/T在四组间分布频率差异有统计学意义(χ2=16.2,P...
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关键词:
- 肝炎,乙型,慢性 /
- 干扰素α /
- 多态性,单核苷酸 /
- 2’,5’寡腺苷酸合成酶
Abstract: Objective To evaluate the role of host single nucleotide polymorphisms (SNPs) of 2′, 5′-oligoadenylate synthetase (OAS) in predicting IFN response in patients with HBeAg-positive chronic HBV infection.Methods OAS gene and four SNPs were examined in 277 patients with HBeAg-positive chronic HBV infection who were treated with IFNα and Nucleotide analogue (NA) .Therapeutic effects were evaluated based on HBsAg and HBeAg seroconversion, resulting in HBsAg seroconversion group, HBeAg seroconversion group, and non-response (NR) group.50 persons with self limiting HBV infection was selected as control.Results Patients reached HBsAg seroconversion were 41 (14.80%) , HBeAg seroconversion were 102 (36.82%) , NR 134 (48.38%) .The frequencies of OAS3 C allele revealed significant association among HBsAg seroconversion, HBeAg seroconversion, NR and control groups (χ2=16.2, P=0.001) .For HBsAg seroconversion and NR, frequency of OAS3 CC+TC genotype is significantly different with an odds ratio (OR) of 3.17 (P=0.07) .The frequency of ACCG and CCTG OAS haplotype were significantly different between non-response and response group (χ2=4.39, P=0.04;χ2=4.89, P=0.03) .Conclusion OAS haplotypes may play an important role in response to IFNα and provide a novel strategy for the resolution of HBsAg and HBeAg seroconversion in patients with HBeAg-positive HBV infections.-
Key words:
- hepatitis B /
- chronic /
- interferon-alpha /
- polymorphism
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