Gut Liver.
2024 Mar;18(2):316-327. 10.5009/gnl230044.
Genetic and Metabolic Characteristics of Lean Nonalcoholic Fatty Liver Disease in a Korean Health Examinee Cohort
- Affiliations
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- 1Department of Family Medicine, Myoungji Hospital, Hanyang University College of Medicine, Goyang, Korea
- 2Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
- 3Departments of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea
- 4Departments of Surgery, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea
- 5Department of Radiology, Hanyang University College of Medicine, Seoul, Korea
- 6Hanyang Institute of Bioscience and Biotechnology, Department of PreMedicine, College of Medicine, Hanyang University, Seoul, Korea
- 7College of Pharmacy, Sahmyook University, Seoul, Korea
- KMID: 2553840
- DOI: http://doi.org/10.5009/gnl230044
Abstract
- Background/Aims
The pathophysiology of lean nonalcoholic fatty liver disease (NAFLD) is unclear but has been shown to be associated with more diverse pathogenic mechanisms than that of obese NAFLD. We investigated the characteristics of genetic or metabolic lean NAFLD in a health checkup cohort.
Methods
This retrospective cross-sectional study analyzed single nucleotide polymorphism data for 6,939 health examinees. Lean individuals were categorized according to a body mass index cutoff of 23 kg/m 2 . Single nucleotide polymorphisms were analyzed using genotyping arrays.
Results
The prevalence of lean NAFLD was 21.6% among all participants with NAFLD, and the proportion of lean NAFLD was 18.5% among lean participants. The prevalence of metabolic syndrome and diabetes among lean patients with NAFLD was 12.4% and 10.4%, respectively. Lean NAFLD appeared to be metabolic-associated in approximately 20.1% of patients. The homozygous minor allele (GG) of PNPLA3 (rs738409) and heterozygous minor alleles (CT, TT) of TM6SF2 (rs58542926) were associated with lean NAFLD. However, the prevalence of fatty liver was not associated with the genetic variants MBOAT7 (rs641738), HSD17B13 (rs72613567), MARC1 (rs2642438), or AGXT2 (rs2291702) in lean individuals. Lean NAFLD appeared to be associated with PNPLA3 or TM6SF2 genetic variation in approximately 32.1% of cases. Multivariate risk factor analysis showed that metabolic risk factors, genetic risk variants, and waist circumference were independent risk factors for lean NAFLD.
Conclusions
In a considerable number of patients, lean NAFLD did not appear to be associated with known genetic or metabolic risk factors. Further studies are required to investigate additional risk factors and gain a more comprehensive understanding of lean NAFLD.
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