HBeAg阳性慢性乙型肝炎患者血清学转换与OAS基因多态性的关联分析  

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

作　　者：任姗[1] 黄雁翔[1] 马丽娜[1] 金怡[1] 何智敏[1] 张晓丹[1] 陈新月[1] 

机构地区：[1]首都医科大学附属北京佑安医院国际医疗部,北京100054

出　　处：《临床肝胆病杂志》2011年第12期1270-1274,共5页Journal of Clinical Hepatology

基　　金：国家"十一五"科技重大专项资助项目(2008ZX10002-013;2008ZX10002-004);国家863项目(2006AA02A410)

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=0.001),携带CC+CT基因型患者与TT基因型分布频率在HBsAg转换组及NR组间存在差异,统计学差异居于临界值(χ2=3.17,P=0.07)。单体型分析显示:单体型ACCG、CCTG在应答组与NR组的分布频率差异有统计学意义(χ2=4.39,P=0.04;χ2=4.89,P=0.03)。结论携带OAS3(rs2072136)C等位基因的HBeAg阳性CHB患者易于获得IFNα治疗HBsAg转换,其单体型可作为获得HBeAg转换的预测因素。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 IFNa and Nucleotide analogue （NA）. Therapeutic effects were evaluated based on HBsAg and I^BeAg 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 serocon- version 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 （X2 = 4. 39, P = 0.04 ; X2 = 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.

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 

分 类 号：R512.62[医药卫生—内科学]