Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma.
Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma.
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DOI：
10.1038/ng.2483
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发表时间：
2013-01
期刊：
影响因子：
30.8
通讯作者：
Yu, Long
中科院分区：
文献类型：
--
作者：
Jiang, De-Ke;Sun, Jielin;Cao, Guangwen;Liu, Yao;Lin, Dongxin;Gao, Yu-Zhen;Ren, Wei-Hua;Long, Xi-Dai;Zhang, Hongxing;Ma, Xiao-Pin;Wang, Zhong;Jiang, Wei;Chen, Tao-Yang;Gao, Yong;Sun, Liang-Dan;Long, Ji-Rong;Huang, Hui-Xing;Wang, Dan;Yu, Hongjie;Zhang, Pengyin;Tang, Li-Sha;Peng, Bo;Cai, Hao;Liu, Ting-Ting;Zhou, Ping;Liu, Fang;Lin, Xiaoling;Tao, Sha;Wan, Bo;Sai-Yin, He-Xi Ge;Qin, Lun-Xiu;Yin, Jianhua;Liu, Li;Wu, Chen;Pei, Yan;Zhou, Yuan-Feng;Zhai, Yun;Lu, Pei-Xin;Tan, Aihua;Zuo, Xian-Bo;Fan, Jia;Chang, Jiang;Gu, Xiaoli;Wang, Neng-Jin;Li, Yang;Liu, Yin-Kun;Zhai, Kan;Zhang, Hongwei;Hu, Zhibin;Liu, Jun;Yi, Qing;Xiang, Yongbing;Shi, Rong;Ding, Qiang;Zheng, Wei;Shu, Xiao-Ou;Mo, Zengnan;Shugart, Yin Yao;Zhang, Xue-Jun;Zhou, Gangqiao;Shen, Hongbing;Zheng, S. Lilly;Xu, Jianfeng;Yu, Long
为了确定中国人群中与B型肝炎病毒（HBV）相关的肝细胞癌（HCC）的遗传易感性位点，我们在2，514例慢性HBV携带者中进行了全基因组关联研究（GWAS（1，161例HCC病例和1，353例对照），然后在6个独立的慢性HBV携带者人群（4，319例病例和4，966例对照）中进行2阶段验证。联合分析显示，HCC风险与两个独立位点显著相关：STAT 4的rs7574865，Pmeta = 2.48 × 10−10，比值比（OR）= 1.21; HLA-DQ的rs 9275319，Pmeta = 2.72 × 10−17，OR = 1.49。rs7574865的危险等位基因G与155例HBV相关HCC患者的HCC组织和非肿瘤组织中较低的STAT 4 mRNA水平显著相关（P趋势分别= 0.0008和0.0002）。我们还发现，与配对的相邻非肿瘤组织相比，HCC肿瘤组织中STAT 4的mRNA表达显著降低（P = 2.33 × 10−14）。
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, Pmeta = 2.48 × 10−10, odds ratio (OR) = 1.21; and rs9275319 at HLA-DQ, Pmeta = 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 (Ptrend = 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).
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影响因子：
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作者：
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