■肝硬化(LC)和肝细胞癌(HCC)是受遗传易感性影响的进展,和持续的乙型肝炎病毒感染也证明遗传易感性。所有HBV相关的结果已平行比较,以确定HBV进展中的风险多态性。
■多阶段关联研究过滤并验证了HBV进展的风险SNP,并探讨了它们与持续感染的关联,中国共有来自三个地点的8906名受试者。使用Cox比例风险模型和Kaplan-MeierLog秩检验来确定与风险SNP相关的进展事件的时间。
■TBX5中的Rs3825214在4个进展队列中复制了与LC和HCC的特定关联,并且与持续感染无关。在3个持续队列中对HBV感染和自然清除的天真。在组合样本中,rs3825214与LC(P<0.001;OR=1.98)和HCC(P<0.001;OR=1.68)的风险增加相关。生物信息学分析结果表明,rs3825214基因型改变了RNA结构和内含子切除率。在571例医院持续HBV感染患者的随访中,93(16.29%)开发了LC,74例(12.96%)进展为HCC,中位随访时间为5.1年。在Cox比例风险模型中,Rs3825214与HCC和LC事件相关(P<0.001)。
■我们确定并证实TBX5的遗传变异与LC和HCC的易感性和发病率显著相关。
UNASSIGNED: Liver cirrhosis (LC) and hepatocellular carcinoma (HCC) are progressions affected by genetic predispositions, and persistent hepatitis B virus infection also demonstrates genetic susceptibility. All HBV-related outcomes have been compared in parallel to identify risk polymorphism in HBV progression.
UNASSIGNED: The multiple-stage association
study filtered and validated the risk SNPs for HBV progression and explored their association with persistent infection, with a total of 8906 subjects in China from three sites. Cox proportional hazards models and Kaplan-Meier Log rank tests were used to determine the time to the progressive event in relation to the risk SNPs.
UNASSIGNED: Rs3825214 in
TBX5 replicated a specific association with LC and HCC in 4 progression cohorts and was not related to persistent infection, naivety to HBV infection and natural clearance in 3 persistent cohorts. In combined samples, rs3825214 was associated with an increased risk of LC (P<0.001; OR = 1.98) and HCC (P<0.001; OR = 1.68). The results of bioinformatics analysis indicated that rs3825214 genotypes change RNA structure and intron excision ratio. In the follow-up of 571 hospital-based persistent HBV infection patients, ninety-three (16.29%) developed LC, and seventy-four (12.96%) progressed to HCC at a median follow-up of 5.1 years. Rs3825214 was associated with HCC and LC events in Cox proportional hazards models (P<0.001).
UNASSIGNED: We identified and confirmed that genetic variants in
TBX5 are significantly associated with susceptibility to and the incidence of LC and HCC.