Journal Article

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

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

2013

Overview

Long Yu and colleagues report a genome-wide association study for hepatitis B virus–related hepatocellular carcinoma (HBV-HCC). They report that genetic variants in STAT4 and HLA-DQ genes confer risk of HBV-HCC. 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 ).

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/208/205/2138 / 631/208/68 / 631/67/1504/1610 / 692/699/1503/1607/234/2513/1549 / Agriculture / Animal Genetics and Genomics / Autoimmune diseases / Biomedicine / Cancer Research / Carcinoma, Hepatocellular - complications / Carcinoma, Hepatocellular - genetics / Carcinoma, Hepatocellular - virology / Confidence intervals / Disease susceptibility / Gene Expression / Gene Function / Genes / Genetic engineering / Genetic Predisposition to Disease / Genetic variance / Genome-Wide Association Study / Genomes / Genotype / Health aspects / Hepatitis B - complications / Hepatitis B - virology / Hepatitis B virus / Hepatitis B virus - genetics / Hepatoma / HLA-DQ Antigens - genetics / Human Genetics / Humans / letter / Life sciences / Liver Neoplasms - complications / Liver Neoplasms - genetics / Liver Neoplasms - virology / Polymorphism, Single Nucleotide / Population / Population control / Quality control / Risk factors / Science / Single nucleotide polymorphisms / STAT4 Transcription Factor - genetics / Studies