Journal
HUMAN MOLECULAR GENETICS
Volume 22, Issue 20, Pages 4233-4238Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddt266
Keywords
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Funding
- Korea Science and Engineering Foundation (KOSEF)
- Korean government (MEST) [2011-0004453]
- Sogang University [SRF-201114006.01]
- SNUH [03-2012-021]
- SK Telecom Research Fund [3420130070]
- Basic Research Laboratory through the National Research Foundation of Korea
- Ministry of Education, Science and Technology [2010-0001200]
- Ministry of Health & Welfare, Republic of Korea [A101023]
- Korea Health Promotion Institute [A101023] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Hepatitis B virus (HBV) infection is the predominant risk factor for chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Recently, several genome-wide association studies(GWASs) of CHB identified human leukocyte antigen (HLA) loci, including HLA-DP and HLA-DQ in Asian populations, as being associated with the risk of CHB. To confirm and identify the host genetic factors related to CHB infection, we performed another GWAS using a higher-density chip in Korean CHB carriers. We analyzed 1400 samples from Korean population (400 CHB cases and 1000 population controls) using a higher-density GWAS chip [1 140 419 single nucleotide polymorphisms (SNPs)]. In subsequent replication analysis, we further analyzed in an independent study of a Korean CHB cohort consisting of 2909 Korean samples (971 cases and 1938 controls). Logistic regression methods were used for statistical analysis adjusting for age and sex as covariates. This study identified two new risk-associated loci for CHB on the HLA region of chromosome 6, e. g. rs652888 on euchromatic histone-lysine-methyltransferase 2 (EHMT2, P = 7.07 x 10(-13)) and rs1419881 on transcription factor 19 (TCF19, P = 1.26 x 10(-18)). Conditional analysis with nearby HLA CHB loci that were previously known, confirmed the independent genetic effects of these two loci on CHB. Conclusion: The GWAS and the subsequent validation study identified new variants associated with the risk of CHB. These findings may advance the understanding of genetic susceptibility to CHB.
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