TBX5 Variants Are Associated with Susceptibility to and the Incidence of Liver Cirrhosis and Hepatocellular Carcinoma in the Chinese Population: A Multicenter and Follow-Up Study

Overview

Journal Infect Drug Resist

Publisher Dove Medical Press

Date 2023 May 9

PMID 37159827

Authors

Jinjian Yao

Xiaochun Mao

Qigang Sun

Biao Wu

Weiling Yu

Yanjing Huang

Shuai Luo

Jia Zeng

Jusheng Lin

Affiliations

Soon will be listed here.

Abstract

Purpose: 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.

Methods: 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.

Results: 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 (<0.001; OR = 1.98) and HCC (<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 (<0.001).

Conclusion: We identified and confirmed that genetic variants in TBX5 are significantly associated with susceptibility to and the incidence of LC and HCC.

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