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Identification of novel OCT 4 genetic variant associated with the risk of chronic hepatitis B in a Korean population
Author(s) -
Shin JoongGon,
Cheong Hyun Sub,
Lee Kwanghyun,
Ju BongGun,
Lee JeongHoon,
Yu Su Jong,
Yoon JungHwan,
Cheong Jae Youn,
Cho Sung Won,
Park Neung Hwa,
Namgoong Suhg,
Kim Lyoung Hyo,
Kim Yoon Jun,
Shin Hyoung Doo
Publication year - 2017
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.13245
Subject(s) - identification (biology) , chronic hepatitis , population , medicine , genetics , genetic variants , hepatitis b , genotype , biology , computational biology , gene , virology , environmental health , virus , botany
Background & Aims Hepatitis B viral infection is a serious risk factor for chronic hepatitis B ( CHB ), cirrhosis and hepatocellular carcinoma. Recently, several genome‐wide association studies ( GWAS s) have been conducted to identify important genetic variant associated with the risk of CHB . In our previous GWAS , TCF 19 was identified as one of the susceptibility genes for CHB risk ( P =4.2×10 −9 at rs1419881 ). In order to discover possible additional causal variants around TCF 19 , we performed an association study by genotyping single nucleotide polymorphisms ( SNP s) in OCT 4 , a nearby gene to TCF 19 . Methods Nineteen OCT 4 genetic variants were selected and genotyped in 3902 subjects (1046 CHB patients and 2856 population controls). Results Logistic regression analysis revealed that OCT 4 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 OCT 4 as a novel genetic marker for CHB susceptibility. The genetic risk scores ( GRS s) were calculated to visualize the combined genetic effects of all known CHB ‐associated loci, including OCT 4 rs1265163 , which had been identified in this study. Individuals with higher cumulative GRS s showed significantly increased OR s. The luciferase activity of rs885952 , a tagging SNP of rs1265163 , showed that OCT 4 promoter activity was significantly different between the wild‐type and SNP mutant form ( P <.05). Conclusions 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 .