TM6SF2-rs58542926 Genetic Variant Modifies the Protective Effect of a Prudent Dietary Pattern on Serum Triglyceride Levels

The epidemic prevalence of non-alcoholic fatty liver disease (NAFLD), despite extensive research in the field, underlines the importance of focusing on personalized therapeutic approaches. However, nutrigenetic effects on NAFLD are poorly investigated. To this end, we aimed to explore potential gene-dietary pattern interactions in a NAFLD case-control study. The disease was diagnosed with liver ultrasound and blood collection was performed after an overnight fast. Adherence to four a posteriori, data-driven, dietary patterns was used to investigate interactions with PNPLA3-rs738409, TM6SF2-rs58542926, MBOAT7-rs641738, and GCKR-rs738409 in disease and related traits. IBM SPSS Statistics/v21.0 and Plink/v1.07 were used for statistical analyses. The sample consisted of 351 Caucasian individuals. PNPLA3-rs738409 was positively associated with disease odds (OR = 1.575, p = 0.012) and GCKR-rs738409 with lnC-reactive protein (CRP) (beta = 0.098, p = 0.003) and Fatty Liver Index (FLI) levels (beta = 5.011, p = 0.007). The protective effect of a Prudent dietary pattern on serum triglyceride (TG) levels in this sample was significantly modified by TM6SF2-rs58542926 (p(interaction) = 0.007). TM6SF2-rs58542926 carriers may not benefit from a diet rich in unsaturated fatty acids and carbohydrates in regard to TG levels, a commonly elevated feature in NAFLD patients.

Automated summary

Despite extensive research, the high prevalence of non-alcoholic fatty liver disease highlights the need for personalized therapeutic approaches. This study explores the gene-dietary pattern interactions in NAFLD and reveals the associations between specific genetic markers and disease odds, as well as related traits such as C-reactive protein and Fatty Liver Index levels. Furthermore, it suggests that the effectiveness of certain dietary patterns on serum triglyceride levels may be influenced by specific genetic variations, particularly TM6SF2-rs58542926.