Replication of genome wide association studies on hepatocellular carcinoma susceptibility loci of STAT4 and HLA-DQ in a Korean population.
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.
Department of Life Science, Sogang University, Republic of Korea; Department of Genetic Epidemiology, SNP Genetics, Inc., Republic of Korea.
Lyoung Hyo
LH
Kim
Department of Genetic Epidemiology, SNP Genetics, Inc., Republic of Korea.
Hyun Sub
HS
Cheong
Department of Life Science, Sogang University, Republic of Korea; Department of Genetic Epidemiology, SNP Genetics, Inc., Republic of Korea.
Suhg
S
Namgoong
Department of Genetic Epidemiology, SNP Genetics, Inc., Republic of Korea.
Ji On
JO
Kim
Department of Life Science, Sogang University, Republic of Korea.
Jeong-Hyun
JH
Kim
Department of Genetic Epidemiology, SNP Genetics, Inc., Republic of Korea.
Byung Lae
BL
Park
Department of Gastroenterology, Ajou University School of Medicine, Republic of Korea.
Sung Won
SW
Cho
Department of Internal Medicine, Ulsan University Hospital, Republic of Korea.
Neung Hwa
NH
Park
Department of Gastroenterology, Ajou University School of Medicine, Republic of Korea.
Jae Youn
JY
Cheong
Department of Physiology, College of Medicine, Han Yang University, Republic of Korea.
InSong
I
Koh
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.
Hyoung Doo
HD
Shin
Department of Internal Medicine and Liver Research Institute, Seoul National University, Republic of Korea. Electronic address: yoonjun@snu.ac.kr.
Yoon-Jun
YJ
Kim
D000483:Alleles; D044466:Asian People / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D012307:Risk Factors; D050797:STAT4 Transcription Factor / Q000235:genetics*
D006683:HLA-DQ Antigens; D050797:STAT4 Transcription Factor
Chronic hepatitis B virus; HLA-DQ; Hepatocellular carcinoma; STAT4