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 Zhang & 44 others Li 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

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HLA-DQ Antigens
Hepatitis B virus
Hepatocellular Carcinoma
Genes
Chronic Hepatitis B
Odds Ratio
Messenger RNA
Genetic Loci
Genome-Wide Association Study
Genetic Predisposition to Disease
Population
Joints
Alleles
Neoplasms

ASJC Scopus subject areas

  • Genetics

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

In: Nature Genetics, Vol. 45, No. 1, 01.2013, p. 72-75.

Research output: Contribution to journalArticle

Jiang, DK, Sun, J, Cao, G, Liu, Y, Lin, D, Gao, YZ, Ren, WH, Long, XD, Zhang, H, Ma, XP, Wang, Z, Jiang, W, Chen, TY, Gao, Y, Sun, LD, Long, JR, Huang, HX, Wang, D, Yu, H, Zhang, P, Tang, LS, Peng, B, Cai, H, Liu, TT, Zhou, P, Liu, F, Lin, X, Tao, S, Wan, B, Sai-Yin, HXG, Qin, LX, Yin, J, Liu, L, Wu, C, Pei, Y, Zhou, YF, Zhai, Y, Lu, PX, Tan, A, Zuo, XB, Fan, J, Chang, J, Gu, X, Wang, NJ, Li, Y, Liu, YK, Zhai, K, Zhang, H, Hu, Z, Liu, J, Yi, Q, Xiang, Y, Shi, R, Ding, Q, Zheng, W, Shu, XO, Mo, Z, Shugart, YY, Zhang, XJ, Zhou, G, Shen, H, Zheng, SL, Xu, J & Yu, L 2013, 'Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma', Nature Genetics, vol. 45, no. 1, pp. 72-75. https://doi.org/10.1038/ng.2483
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. / Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma. In: Nature Genetics. 2013 ; Vol. 45, No. 1. pp. 72-75.
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title = "Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma",
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).",
author = "Jiang, {De Ke} and Jielin Sun and Guangwen Cao and Yao Liu and Dongxin Lin and Gao, {Yu Zhen} and Ren, {Wei Hua} and Long, {Xi Dai} and Hongxing Zhang and Ma, {Xiao Pin} and Zhong Wang and Wei Jiang and Chen, {Tao Yang} and Yong Gao and Sun, {Liang Dan} and Long, {Ji Rong} and Huang, {Hui Xing} and Dan Wang and Hongjie Yu and Pengyin Zhang and Tang, {Li Sha} and Bo Peng and Hao Cai and Liu, {Ting Ting} and Ping Zhou and Fang Liu and Xiaoling Lin and Sha Tao and Bo Wan and Sai-Yin, {He Xi Ge} and Qin, {Lun Xiu} and Jianhua Yin and Li Liu and Chen Wu and Yan Pei and Zhou, {Yuan Feng} and Yun Zhai and Lu, {Pei Xin} and Aihua Tan and Zuo, {Xian Bo} and Jia Fan and Jiang Chang and Xiaoli Gu and Wang, {Neng Jin} and Yang Li and Liu, {Yin Kun} and Kan Zhai and Hongwei Zhang and Zhibin Hu and Jun Liu and Qing Yi and Yongbing Xiang and Rong Shi and Qiang Ding and Wei Zheng and Shu, {Xiao Ou} and Zengnan Mo and Shugart, {Yin Yao} and Zhang, {Xue Jun} and Gangqiao Zhou and Hongbing Shen and Zheng, {S. Lilly} and Jianfeng Xu and Long Yu",
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AU - Sun, Jielin

AU - Cao, Guangwen

AU - Liu, Yao

AU - Lin, Dongxin

AU - Gao, Yu Zhen

AU - Ren, Wei Hua

AU - Long, Xi Dai

AU - Zhang, Hongxing

AU - Ma, Xiao Pin

AU - Wang, Zhong

AU - Jiang, Wei

AU - Chen, Tao Yang

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AU - Liu, Ting Ting

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AU - Lin, Xiaoling

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AU - Sai-Yin, He Xi Ge

AU - Qin, Lun Xiu

AU - Yin, Jianhua

AU - Liu, Li

AU - Wu, Chen

AU - Pei, Yan

AU - Zhou, Yuan Feng

AU - Zhai, Yun

AU - Lu, Pei Xin

AU - Tan, Aihua

AU - Zuo, Xian Bo

AU - Fan, Jia

AU - Chang, Jiang

AU - Gu, Xiaoli

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AU - Liu, Yin Kun

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AU - Yi, Qing

AU - Xiang, Yongbing

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AU - Ding, Qiang

AU - Zheng, Wei

AU - Shu, Xiao Ou

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AU - Shugart, Yin Yao

AU - Zhang, Xue Jun

AU - Zhou, Gangqiao

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AU - Zheng, S. Lilly

AU - Xu, Jianfeng

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N2 - 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).

AB - 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).

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