Identification of novel OCT4 genetic variant associated with the risk of chronic hepatitis B in a Korean population.
Hepatitis B viral infection is a serious risk factor for chronic hepatitis B (CHB), cirrhosis and hepatocellular carcinoma. Recently, several genome-wide association studies (GWASs) have been conducted to identify important genetic variant associated with the risk of CHB. In our previous GWAS, TCF19 was identified as one of the susceptibility genes for CHB risk (P=4.2×10-9at rs1419881). In order to discover possible additional causal variants around TCF19, we performed an association study by genotyping single nucleotide polymorphisms (SNPs) in OCT4, a nearby gene to TCF19.



Nineteen OCT4 genetic variants were selected and genotyped in 3902 subjects (1046 CHB patients and 2856 population controls).



Logistic regression analysis revealed that OCT4 rs1265163 showed the most significant association signal for the risk of CHB (OR=1.46, P=4.78×10-12). Linkage disequilibrium and conditional analysis confirmed rs1265163 in OCT4 as a novel genetic marker for CHB susceptibility. The genetic risk scores (GRSs) were calculated to visualize the combined genetic effects of all known CHB-associated loci, including OCT4 rs1265163, which had been identified in this study. Individuals with higher cumulative GRSs showed significantly increased ORs. The luciferase activity of rs885952, a tagging SNP of rs1265163, showed that OCT4 promoter activity was significantly different between the wild-type and SNP mutant form (P<.05).



This follow-up study to our previous GWAS identified a possible causal genetic variant associated with the risk of CHB, and findings from this study may prove useful in the understanding of genetic susceptibility to CHB.
Department of Life Science, Sogang University, Seoul, Korea.|Research Institute for Basic Science, Sogang University, Seoul, Korea.
Joong-Gon
JG
Shin
Department of Genetic Epidemiology, SNP Genetics Inc., Sogang University, Seoul, Korea.
Hyun Sub
HS
Cheong
Department of Life Science, Sogang University, Seoul, Korea.
Kwanghyun
K
Lee
Department of Life Science, Sogang University, Seoul, Korea.|Research Institute for Basic Science, Sogang University, Seoul, Korea.
Bong-Gun
BG
Ju
Department of Internal Medicine and Liver Research Institute, Seoul National University, Seoul, Korea.
Jeong-Hoon
JH
Lee
Department of Internal Medicine and Liver Research Institute, Seoul National University, Seoul, Korea.
Su Jong
SJ
Yu
Department of Internal Medicine and Liver Research Institute, Seoul National University, Seoul, Korea.
Jung-Hwan
JH
Yoon
Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
Jae Youn
JY
Cheong
Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.
Sung Won
SW
Cho
Department of Internal Medicine, Ulsan University Hospital, Ulsan, Korea.
Neung Hwa
NH
Park
Department of Life Science, Sogang University, Seoul, Korea.|Department of Genetic Epidemiology, SNP Genetics Inc., Sogang University, Seoul, Korea.
Suhg
S
Namgoong
Department of Life Science, Sogang University, Seoul, Korea.|Department of Genetic Epidemiology, SNP Genetics Inc., Sogang University, Seoul, Korea.
Lyoung Hyo
LH
Kim
Department of Internal Medicine and Liver Research Institute, Seoul National University, Seoul, Korea.
Yoon Jun
YJ
Kim
Department of Life Science, Sogang University, Seoul, Korea.|Research Institute for Basic Science, Sogang University, Seoul, Korea.|Department of Genetic Epidemiology, SNP Genetics Inc., Sogang University, Seoul, Korea.
Hyoung Doo
HD
Shin
D000328:Adult; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D050814:Octamer Transcription Factor-3 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D018570:Risk Assessment; D012307:Risk Factors
D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human

OCT4
; Korean population; Single nucleotide polymorphism; chronic hepatitis B