Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma

De Ke Jiang, Jielin Sun, Guangwen Cao, Yao Liu, Dongxin Lin, Yu Zhen Gao, Wei Hua Ren, Xi Dai Long, Hongxing Zhang, Xiao Pin Ma, Zhong Wang, Wei Jiang, Tao Yang Chen, Yong Gao, Liang Dan Sun, Ji Rong Long, Hui Xing Huang, Dan Wang, Hongjie Yu, Pengyin ZhangLi Sha Tang, Bo Peng, Hao Cai, Ting Ting Liu, Ping Zhou, Fang Liu, Xiaoling Lin, Sha Tao, Bo Wan, He Xi Ge Sai-Yin, Lun Xiu Qin, Jianhua Yin, Li Liu, Chen Wu, Yan Pei, Yuan Feng Zhou, Yun Zhai, Pei Xin Lu, Aihua Tan, Xian Bo Zuo, Jia Fan, Jiang Chang, Xiaoli Gu, Neng Jin Wang, Yang Li, Yin Kun Liu, Kan Zhai, Hongwei Zhang, Zhibin Hu, Jun Liu, Qing Yi, Yongbing Xiang, Rong Shi, Qiang Ding, Wei Zheng, Xiao Ou Shu, Zengnan Mo, Yin Yao Shugart, Xue Jun Zhang, Gangqiao Zhou, Hongbing Shen, S. Lilly Zheng, Jianfeng Xu, Long Yu

Research output: Contribution to journalArticle

Abstract

To identify genetic susceptibility loci for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in the Chinese population, we carried out a genome-wide association study (GWAS) in 2,514 chronic HBV carriers (1,161 HCC cases and 1,353 controls) followed by a 2-stage validation among 6 independent populations of chronic HBV carriers (4,319 cases and 4,966 controls). The joint analyses showed that HCC risk was significantly associated with two independent loci: rs7574865 at STAT4, P meta = 2.48 × 10 -10, odds ratio (OR) = 1.21; and rs9275319 at HLA-DQ, P meta = 2.72 × 10 -17, OR = 1.49. The risk allele G at rs7574865 was significantly associated with lower mRNA levels of STAT4 in both the HCC tissues and nontumor tissues of 155 individuals with HBV-related HCC (P trend = 0.0008 and 0.0002, respectively). We also found significantly lower mRNA expression of STAT4 in HCC tumor tissues compared with paired adjacent nontumor tissues (P = 2.33 × 10 -14).

Original languageEnglish (US)
Pages (from-to)72-75
Number of pages4
JournalNature genetics
Volume45
Issue number1
DOIs
StatePublished - Jan 2013

ASJC Scopus subject areas

  • Genetics

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