蛋白磷酸酶1调节亚基11基因多态性与丙型肝炎病毒自发清除的相关性分析

目的 探讨蛋白磷酸酶1调节亚基11（PPP1R11）基因多态性与丙型肝炎病毒（HCV）感染自发清除的相关性.方法 选择2009年1月至2013年5月于广州血液中心行无偿献血的献血者中,血液样品HCV抗体的酶联免疫吸附试验（ELISA）检测结果呈阳性的328例献血者为研究对象.将研究对象随访结果中,HCV RNA检测结果呈阴性,但经重组免疫印迹试验（RIBA）确证为HCV抗体呈阳性献血者纳入自发清除组（n=134）;HCV RNA检测结果呈阳性献血者纳入慢性感染组（n=194）.采用序列特异性引物聚合酶链反应（PCR-SSP）检测PPP1 R11基因rs3807031位点基因型,分析其与HCV自发清除的相关性.结果 自发清除组献血者的平均年龄为（28.8±10.2）岁低于慢性感染组的（31.0±9.0）岁.二者比较,差异有统计学意义（t=2.135,P=0.034）.自发清除组中女性比例为35.8％,高于慢性感染组的21.6％.二者比较,差异有统计学意义（x2 =7.994,P=0.005）. rs3807031的等位基因A和C在自发清除组的基因频率分别为30.6％和69.4％,在慢性感染组中则为22.4％和77.6％.两组献血者rs3807031等位基因频率比较,差异有统计学意义（x2 =5.538,P=0.023）.多因素非条件logistic回归分析结果表明,性别（OR=1.957,95％CI：1.118～3.224,P=0.008）和rs3807031基因型（OR=0.650,95％CI：0.450～0.973,P=0.021）是HCV自发清除的独立影响因素.结论 PPP1R11基因rs3807031位点基因型与HCV自发清除显著相关,可作为HCV感染自发清除的预测因素,为进一步研究机体自发清除HCV的机制及分子标志物提供了科学证据.

Correlation Analysis Between Protein Phosphatase-1 Regulatory Inhibitor Subunit-11 Polymorphism and Hepatitis C Virus Spontaneous Clearance

Objective To explore the association of protein phosphatase-1 regulatory inhibitor subunit-11 （PPP1R11） polymorphism and hepatitis C virus （HCV） spontaneous clearance.Methods From January 2009 to May 2013,a total of 328 blood donors whose blood samples were anti-HCV positive with enzyme-linked immunosorbent assay （ELISA） were included into this study.According to follow-up results,they were divided into spontaneous clearance group whose HCV RNA were negative but anti-HCV recombinant immunoblot assay results were positive （n =134）,and chronic infection group whose HCV RNA were positive （n=198）.Polymerase chain reaction with sequence specific primer（PCR-SSP） was performed to determine the genotype of rs3807031 of PPP1R11.Statistical software SPSS was used to analyze the association between genotype of rs3807031 and HCV spontaneous clearance.Results The average age of donors in spontaneous clearance group was （28.8± 10.2） years old,which was significantly lower than that of chronic infection group whose average age was （31.0±9.0） years old （t=2.135,P =0.034）.Higher percentage of female was observed in spontaneous clearance group compared to chronic infection group （35.8％ vs 21.6％ ; x2 =7.994,P=0.005）.Importantly,rs3807031 A allele composed 30.6％ and 22.4％,while C allele composed 69.4％ and 77.6％ in spontaneous clearance and chronic infection group,respectively.The frequencies of rs3807031 alleles were statistically different between these two groups （x2 =5.538,P =0.023）.Multivariate unconditional logistic regression analysis showed that gender （OR=1.957,95％CI：1.118-3.224,P=0.008） and genotype of rs3807031 （OR=0.650,95％CI：0.450-0.973,P =0.021） are independent factors associated with HCV spontaneous clearance.Conclusions PPP1R11 rs3807031 is associated with HCV spontaneous clearance,which has the potential to predict the spontaneous clearance of HCV infection.Our results provide information to the research on the mechanism and molecular marker of