Genome-wide association study of metabolic dysfunction-associated fatty liver disease in a Korean population.

Autor: Lee Y; Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul, Republic of Korea.; Department of Applied Statistics, Chung-Ang University, Seoul, Republic of Korea., Cho EJ; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea., Choe EK; Department of Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea., Kwak MS; Department of Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea., Yang JI; Department of Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea., Oh SW; Department of Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea.; Department of Family Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul National University College of Medicine, Seoul, Republic of Korea., Yim JY; Department of Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea., Chung GE; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. gohwom@snu.ac.kr.; Department of Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea. gohwom@snu.ac.kr.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Apr 29; Vol. 14 (1), pp. 9753. Date of Electronic Publication: 2024 Apr 29.
DOI: 10.1038/s41598-024-60152-0
Abstrakt: Genome-wide association studies have identified several genetic variants associated with nonalcoholic fatty liver disease. To emphasize metabolic abnormalities in fatty liver, metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been introduced; thus, we aimed to investigate single-nucleotide polymorphisms related to MAFLD and its subtypes. A genome-wide association study was performed to identify genetic factors related to MAFLD. We used a Korean population-based sample of 2282 subjects with MAFLD and a control group of 4669. We replicated the results in a validation sample which included 639 patients with MAFLD and 1578 controls. Additionally, we categorized participants into three groups, no MAFLD, metabolic dysfunction (MD)-MAFLD, and overweight/obese-MAFLD. After adjusting for age, sex, and principal component scores, rs738409 [risk allele G] and rs3810622 [risk allele T], located in the PNPLA3 gene, showed significant associations with MAFLD (P-values, discovery set = 1.60 × 10 -15 and 4.84 × 10 -10 ; odds ratios, 1.365 and 1.284, validation set = 1.39 × 10 -4 , and 7.15 × 10 -4 , odds ratios, 1.299 and 1.264, respectively). An additional SNP rs59148799 [risk allele G] located in the GATAD2A gene showed a significant association with MAFLD (P-values, discovery set = 2.08 × 10 -8 and validation set = 0.034, odds ratios, 1.387 and 1.250). rs738409 was significantly associated with MAFLD subtypes ([overweight/obese-MAFLD; odds ratio (95% confidence interval), P-values, 1.515 (1.351-1.700), 1.43 × 10 -12 and MD-MAFLD: 1.300 (1.191-1.416), 2.90 × 10 -9 ]. There was a significant relationship between rs3810622 and overweight/obese-MAFLD and MD-MAFLD [odds ratios (95% confidence interval), P-values, 1.418 (1.258, 1.600), 1.21 × 10 -8 and 1.225 (1.122, 1.340), 7.06 × 10 -6 , respectively]; the statistical significance remained in the validation set. PNPLA3 was significantly associated with MAFLD and MAFLD subtypes in the Korean population. These results indicate that genetic factors play an important role in the pathogenesis of MAFLD.
(© 2024. The Author(s).)
Databáze: MEDLINE
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