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Infect Genet Evol. 2015;33:72-6.

Replication of genome wide association studies on hepatocellular carcinoma susceptibility loci of STAT4 and HLA-DQ in a Korean population.

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제1저자 김령효 · 교신저자 김윤준

소속 (8)
  1. Department of Life Science, Sogang University, Republic of Korea; Department of Genetic Epidemiology, SNP Genetics, Inc., Republic of Korea.
  2. Department of Genetic Epidemiology, SNP Genetics, Inc., Republic of Korea.
  3. Department of Life Science, Sogang University, Republic of Korea.
  4. Department of Gastroenterology, Ajou University School of Medicine, Republic of Korea.
  5. Department of Internal Medicine, Ulsan University Hospital, Republic of Korea.
  6. Department of Physiology, College of Medicine, Han Yang University, Republic of Korea.
  7. Department of Life Science, Sogang University, Republic of Korea; Department of Genetic Epidemiology, SNP Genetics, Inc., Republic of Korea. Electronic address: hdshin@sogang.ac.kr.
  8. Department of Internal Medicine and Liver Research Institute, Seoul National University, Republic of Korea. Electronic address: yoonjun@snu.ac.kr.

Abstract

A recent genome-wide association study (GWAS) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) identified two loci (rs7574865 in STAT4 and rs9275319 in HLA-DQ) in a Chinese population. We attempted to replicate the associations between the two SNP loci and the risk of HCC in a Korean population. The rs7574865 in STAT4 and rs9275319 in HLA-DQ were genotyped in a total of 3838 Korean subjects composed of 287 HBV-related hepatocellular carcinoma patients, 671 chronic hepatitis B virus (CHB) patients, and 2880 population controls using TaqMan genotyping assay. Gene expression was measured by microarray. A logistic regression analysis revealed that rs7574865 in STAT4 and rs9275319 in HLA-DQ were associated with the risk of CHB (OR = 1.25, P = 0.0002 and OR = 1.57, P= 1.44 × 10(-10), respectively). However, these loci were no association with the risk of HBV-related HCC among CHB patients. In the gene expression analyses, although no significant differences in mRNA expression of nearby genes according to genotypes were detected, a significantly decreased mRNA expression in HCC subjects was observed in STAT4, HLA-DQA1, and HLA-DQB1. Although the genetic effects of two HCC susceptibility loci were not replicated, the two loci were found to exert susceptibility effects on the risk of CHB in a Korean population. In addition, the decreased mRNA expression of STAT4, HLA-DQA1, and HLA-DQB1 in HCC tissue might provide a clue to understanding their role in the progression to HCC.

Copyright © 2015 Elsevier B.V. All rights reserved.

Keywords

Chronic hepatitis B virusHLA-DQHepatocellular carcinomaSTAT4

그 밖의 정보
출판 형태
Journal Article
저널
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · eISSN 1567-7257
전자 출판
2015-04-22
MeSH
Alleles · Asian People / genetics · Carcinoma, Hepatocellular / epidemiology / genetics · Case-Control Studies · Female · Gene Expression · Gene Frequency · Genetic Loci · Genetic Predisposition to Disease* · Genome-Wide Association Study* · Genotype · HLA-DQ Antigens / genetics · Humans · Liver Neoplasms / epidemiology / genetics · Male · Polymorphism, Single Nucleotide · Republic of Korea · Risk Factors · STAT4 Transcription Factor / genetics
Substances
HLA-DQ Antigens · STAT4 Transcription Factor