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Genome-wide association of individual vulnerability with alcohol-associated liver disease: A Korean genome and epidemiology study

Authors
 Kwang Yoon Kim  ;  Jung Oh Kim  ;  Young-Sang Kim  ;  Ja-Eun Choi  ;  Jae-Min Park  ;  Kunhee Han  ;  Da-Hyun Park  ;  Yon Chul Park  ;  Bom Taeck Kim  ;  Kyung-Won Hong 
Citation
 HEPATOLOGY, Vol.75(2) : 391-402, 2022-02 
Journal Title
HEPATOLOGY
ISSN
 0270-9139 
Issue Date
2022-02
MeSH
Adult ; Aged ; Alcohol Drinking / epidemiology ; Alleles ; Case-Control Studies ; DNA-Binding Proteins / genetics* ; Female ; Genetic Predisposition to Disease / epidemiology* ; Genome-Wide Association Study ; Hepatocyte Nuclear Factor 1-alpha / genetics* ; Humans ; Liver Diseases, Alcoholic / epidemiology* ; Liver Diseases, Alcoholic / genetics* ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Republic of Korea / epidemiology ; Risk Assessment ; Risk Factors ; gamma-Glutamyltransferase / genetics*
Abstract
Background and aims: The quantity of alcohol leading to alcohol-associated liver disease (ALD) varies individually. Genetic backgrounds contributing to the divergence in individual susceptibility to alcohol-induced liver damage have not been elucidated in detail.

Approach and results: Based on the Korean Genome and Epidemiology Study Health Examination (KoGES_HEXA) cohort data, 21,919 participants (40-79 years old) were included and divided into cases and controls based on the ALD diagnostic criteria proposed by the American College of Gastroenterology. Data generated by a genome wide-association study were analyzed using logistic regression to assess the risk of ALD development in nondrinkers, light drinkers, and heavy drinkers. We detected three loci, gamma-glutamyltransferase 1 (GGT1), zinc protein finger 827 (ZNF827) and HNF1 homeobox A (HNF1A), which were significantly associated with ALD risk. The GGT1 rs2006227 minor allele was strongly associated with all groups. Among the minor alleles of single nucleotide polymorphisms (SNPs) in HNF1A, rs1183910 had the strongest association with a protective effect from ALD in light drinkers. However, this association was not observed in heavy drinkers. Five SNPs on chromosome 11 showed suggestive significance in protective effects against ALD.

Conclusions: SNPs, including HNF1A rs1183910 minor allele, are the most promising genetic candidates for protection against ALD. The expression of genes contributing to ALD development may be altered by the amount of alcohol consumed.
Full Text
https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.32115
DOI
10.1002/hep.32115
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Family Medicine (가정의학교실) > 1. Journal Papers
Yonsei Authors
Park, Jae Min(박재민) ORCID logo https://orcid.org/0000-0001-8873-8832
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/187980
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