Genetic Variants Linked to Myocardial Infarction in Individuals with Non-Alcoholic Fatty Liver Disease and Their Potential Interaction with Dietary Patterns

Abstract

In recent studies, non-alcoholic fatty liver disease (NAFLD) has been associated with a high risk of ischemic heart disease. This study aimed to investigate a genetic variant within a specific gene associated with myocardial infarction (MI) among patients with NAFLD. We included 57,205 participants from a Korean genome and epidemiology study. The baseline population consisted of 45,400 individuals, with 11,805 identified as patients with NAFLD. Genome-wide association studies were conducted for three groups: the entire sample, the healthy population, and patients with NAFLD. We defined the p-value < 1 × 10−5 as the nominal significance and the p-value < 5 × 10−2 as statistically significant for the gene-by-nutrient interaction. Among the significant single-nucleotide polymorphisms (SNPs), the lead SNP of each locus was further analyzed. In this cross-sectional study, a total of 1529 participants (2.8%) had experienced MI. Multivariable logistic regression was performed to evaluate the association of 102 SNPs across nine loci. Nine SNPs (rs11891202, rs2278549, rs13146480, rs17293047, rs184257317, rs183081683, rs1887427, rs146939423, and rs76662689) demonstrated an association with MI in the group with NAFLD Notably, the MI-associated SNP, rs134146480, located within the SORCS2 gene, known for its role in secreting insulin in islet cells, showed the most significant association with MI (p-value = 2.55 × 10−7). Our study identifies candidate genetic polymorphisms associated with NAFLD-related MI. These findings may serve as valuable indicators for estimating MI risk and for conducting future investigations into the underlying mechanisms of NAFLD-related MI.