摘要目的 探讨胆固醇7α-羟化酶(CYP7A1)基因多态性与福建汉族人HBV感染后不同临床结局之间的相关性,为了解HBV相关疾病的发生发展机制奠定基础.方法 病例对照研究.收集2015年5月至2016年6月在福建医科大附属第一医院肝病中心未经抗病毒治疗的HBV持续感染者586例,乙型肝炎康复者225例(年龄在35~55岁之间).未经抗病毒治疗的HBV持续感染组包括慢性乙型肝炎患者亚组(246例)、乙型肝炎相关性肝硬化亚组(177例)和乙肝相关性肝癌亚组(163例).采用改良的多重高温连接酶检测反应技术(iMLDR)对CYP7A1基因的rs3824260、rs4738687和rs8192871位点进行检测,在HBV持续感染组、乙型肝炎康复组以及慢性乙型肝炎亚组、肝硬化亚组和肝癌亚组之间进行两两比较,校正年龄性别因素运用二分类Logistic回归模型和卡方检验分析基因分型结果.结果 rs3824260位点各基因型在各组间的分布差异无统计学意义(χ2=1.565,P=0.459),然而在性别分层后,男性分组中乙型肝炎康复组的C等位基因频率明显高于HBV持续感染组(χ2=4.365,P=0.037),女性分组中,相较于非肝癌组(慢乙肝亚组和肝硬化亚组),rs3824260 CC+CT等位基因更多见于肝癌亚组患者(χ2=5.768,P=0.012;χ2=10.130,P=0.001);相较于肝癌组,rs4738687的突变型GG基因型频率在非肝癌组中显著增高(χ2=4.403,P=0.041;χ2=6.940, P=0.009),性别分层结果显示男性分组的rs4738687的各基因型在HBV持续感染组间的分布差异有统计学意义(χ2=10.697,P=0.030),但在女性分组中该位点基因型分布差异无统计学意义(χ2=4.627,P=0.329);rs8192871位点的各基因型频率及等位基因频率在各组间的分布差异均无统计学意义(χ2=0.489,P=0.792),性别分层后差异也无统计学意义(χ2=1.282,P=0.526;χ2=1.565, P=0.465).结论 CYP7A1基因多态性与福建汉族HBV感染者的不同临床结局有关.rs3824260位点突变具有一定的性别倾向,在男性患者中突变等位基因检出比例更高,携带rs3824260 C等位基因的男性乙型肝炎患者更有机会转为乙肝康复;rs4738687位点可能与福建汉族人肝癌的发生有关,尤其是在男性分组中,GG基因型可能会延缓肝癌的发生发展;未发现rs8192871位点与HBV感染的不同临床结局存在相关性.

abstractsObjective The study aims to investigate the associationbetweencholesterol 7α-hydroxylase (CYP7A1) gene polymorphism and different clinical outcomes after Hepatitis B virus (HBV)infection in Fujian Han population and lay a foundation for understanding the mechanisms of genesis anddevelopment of HBV-related diseases.Methods Case-control study was conducted.586 patients of HBVpersistent infection without antiviral therapy and 225 HBV rehabilitation patients (35-55 years old) werecollected from May 2015 to June 2016 in the Liverish Center of First Clinical College of Fujian MedicalUniversity.The group of HBV persistent infection without antiviral therapy included 246 patients with chronichepatitis B, 177 patients with hepatitis B-related cirrhosis, and 163 patients with hepatitis B-related liver cancer.The rs3824260, rs4738687and rs8192871 loci of CYP7A1 gene were detected by improved multipleligase detection reaction (iMLDR).Logistic regression analysis and chi-square test were used to analyze thegenotyping results.Results Three SNPs ( single nucleotide polymorphisms ) of CYP7A1 gene wereselected and compared between HBV persistent infection group and HBV rehabilitation group and betweenchronic hepatitis B subgroup, liver cirrhosis subgroup and liver cancer subgroup.After adjustment for factorsincluding age andgender, there was no significant difference in the distribution of rs3824260 genotype amongthe groups(χ2 =1.565,P =0.459), however,the frequency of allele C in HBV rehabilitation group wassignificantly higher than in HBV persistent in fectiongroup for men (χ2 =4.365,P =0.037), whereas thefrequency of rs3824260 CC and CT was more likely to be observed in liver cancer group than in non -livercancer group (chronic hepatitis B subgroup and liver cirrhosis subgroup ) for women (χ2 =5.768,P =0.012;χ2 =10.130,P =0.001).The frequency of rs4738687 GG genotype was more likely to be observed innon-liver cancer group than in liver cancer group (χ2 =4.403,P =0.041;χ2 =6.940,P =0.009).Theresults of gender stratification showed that there were significant differences in the distribution of rs 4738687among the HBV persistent infection groups for men (χ2 =10.697,P =0.030), however, there was nosignificant difference in the distribution of rs4738687 among the HBV persistent infection groups for women(χ2 =4.627,P =0.329), and there was no significant difference in the distribution of genotype frequencyand allele frequency among all groups(χ2 =0.489,P =0.792).There was no significant difference after sexstratification either (χ2 =1.282, P =0.526;χ2 =1.565,P =0.465) .Conclusions These findingssuggested that CYP7A1 gene polymorphism was related todifferent clinical outcomes in Fujian Hanpopulation.The rs3824260 mutation had a certain gender preference and the mutation allele was detected ina higher proportion in male patients.Male HBV patients with rs3824260 C allele had more chance ofswitching to rehabilitation.The rs4738687 was likely to be related to the occurrence of liver cancer in FujianHan population, and GG genotype may delay the occurrence and development of liver cancer especially in themale group.The rs8192871 was not found to be related to the different clinical outcomes of HBV infection.