The association of genetic polymorphisms with nonalcoholic fatty liver disease in a longitudinal study
- PDF / 1,144,919 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 38 Downloads / 178 Views
RESEARCH ARTICLE
Open Access
The association of genetic polymorphisms with nonalcoholic fatty liver disease in a longitudinal study Goh Eun Chung1*† , Eunsoon Shin2†, Min-Sun Kwak1, Jong In Yang1, Jong-Eun Lee2, Eun Kyung Choe3 and Jeong Yoon Yim1
Abstract Background: Several genetic variants are known to be associated with nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the longitudinal associations between genetic variants and NAFLD. Methods: We performed a genome-wide association study (GWAS) in Korean individuals who underwent repeated health check-ups. NAFLD was defined by ultrasonography and exclusion of secondary causes. Results: The subjects had a median age of 50.0 years, and 54.8% were male. The median follow-up duration was 39 months. Among the 3905 subjects without NAFLD at baseline, 874 (22.4%) subjects developed NAFLD, and among the 1818 subjects with NAFLD at baseline, NAFLD regressed in 336 (18.5%) subjects during the follow-up period. After adjusting for age, sex and body mass index, no single-nucleotide polymorphism (SNP) passed Bonferroni correction for genome-wide significance in the development or regression of NAFLD. Among the SNPs that passed the genome-wide suggestiveness threshold (p = 1E-04) in the discovery set in the GWAS, only 1 SNP (rs4906353) showed an association with the development of NAFLD, with marginal significance in the validation set (p-value, discovery set = 9.68E-5 and validation set = 0.00531). Conclusions: This exploratory study suggests that longitudinal changes in NAFLD are not associated with genetic variants in the Korean population. These findings provide new insight into genetic mechanisms in the pathogenesis of NAFLD. Keywords: Nonalcoholic fatty liver disease, Genome-wide association study, Single-nucleotide polymorphism
Background Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in the world, with an increasing prevalence of up to 20–30% in the general population [1]. While the majority of NAFLD patients follow a relatively benign clinical course, with simple hepatic steatosis or mild nonalcoholic steatohepatitis, * Correspondence: [email protected] † Goh Eun Chung and Eunsoon Shin contributed equally to this work. 1 Department of Internal Medicine, Gangnam Healthcare Center, Seoul National University Hospital, 39FL., Gangnam Finance center 737, Yeoksam-Dong, Gangnam-Gu, Seoul 135-984, South Korea Full list of author information is available at the end of the article
approximately 25% of patients may experience progression to advanced liver disease and have increased liver-related mortality [2–4]. In Asia, the annual incidence of hepatocellular carcinoma and the overall mortality in patients with NAFLD are increasing, with few effective treatments [5]. NAFLD development is driven by environmental factors, but it also requires genetic susceptibility [6, 7]. Previous genome-wide association studies (GWASs) have identified a variety of genes and single-nucleotide polymorphisms (SNPs) that confer susceptibil
Data Loading...
