Genome‐wide association of individual vulnerability with alcohol‐associated liver disease: A Korean genome and epidemiology study
| Autor: | Kyung-Won Hong, Jung Oh Kim, Yon Chul Park, Ja-Eun Choi, Da-Hyun Park, Bom-Taeck Kim, Young-Sang Kim, Kunhee Han, Kwang Yoon Kim, Jae-Min Park |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male endocrine system Alcoholic liver disease medicine.medical_specialty Alcohol Drinking Genome-wide association study Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Risk Assessment Genome Risk Factors Republic of Korea Epidemiology medicine Humans Genetic Predisposition to Disease Hepatocyte Nuclear Factor 1-alpha Allele Liver Diseases Alcoholic Alleles Aged Genetics Hepatology gamma-Glutamyltransferase Middle Aged medicine.disease DNA-Binding Proteins Minor allele frequency Case-Control Studies Cohort Female Genome-Wide Association Study |
| Zdroj: | Hepatology. 75:391-402 |
| ISSN: | 1527-3350 0270-9139 |
| DOI: | 10.1002/hep.32115 |
| Popis: | 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.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.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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text