组合分析法探讨HLA-DRB1、-DQA1等位基因与乙型肝炎病毒感染结局的关系

Association of HLA-DRBI and HLA-DQAI genes with outcome of hepatitis B virus infection

目的采用组合分析法探讨中国北方汉族人群HLA-DRB1、-DQA1等位基因与乙型肝炎病毒(hepatitis B virus,HBV)感染不同结局的关系。方法采用序列特异性引物多聚酶链式反应(PCR-SSP)技术对207名慢性乙型肝炎患者和148名自限性HBV感染者进行HLA-DRB1、DQA1等位基因的检测,并运用病例对照研究设计和组合分析法比较HLA-DRB1、-DQA1等位基因与HBV感染不同结局的关系。结果携带HLA-DQA1*0102或HLA-DQA1*0301等位基因者,感染HBV后发展为慢性乙肝的风险显著低于不携带这些等位基因者,比值比(odds ratio,OR)分别为0.23和0.52。用此两个等位基因进行组合分析发现,仅携带HLA-DQA1*0102或HLA-DQA1*0301任何一个等位基因者,较不携带HLA-DQA1*0102和HLA-DQA1*0301两个等位基因者发展为慢性乙肝的风险显著降低(OR=0.28,x^2=31.16,P<0.0001),而同时携带HLA-DQA1*0102和HLA-DQA1*0301两等位基因者,发展为慢性乙肝的风险降低则更为明显(OR=0.16,x^2=5.86,P=0.02)。结论具有两个保护(或危险)作用的等位基因者比不具有或仅有其中一个等位基因者对HBV感染的结局影响更大。

Objective To explore the potential association of HLA-DRB1 and HLA-DQA1 alleles with outcome of hepatitis B virus infection in Han population of north China by combination analysis. Methods Two hundred and seven chronic hepatitis B patients and 148 serf-limited HBV infection subjects were investigated for HLA-DRB1 and HLA-DQA1 allele by PCR-SSP. The association was analyzed by combination analysis, based on case-control study design and combination analysis. Results The frequency of HLA-DQA1 ＊ 0102, HLA-DQA1 0301 in chronic hepatitis B patients were significantly lower than that in self-limited HBV infection subjects （OR = 0.23, OR = 0.52）. Compared with the subjects who had HLA-DQA1 ＊ 0102 allele or HLA-DQA1 ＊ 0301 allele （OR = 0.28, X^2 = 31.16, P 〈 0.0001 ）, the people with HLA-DQA1 ＊ 0102 and HLA-DQA1 ＊ 0301 alleles were not prone to become chronic hepatitis B （OR = 0.16, X^2= 5.86, P = 0.02）. Conclusion The subjects with two protective （or risk） alleles had higher value of OR for the outcome of HBV infection.