Association of the TM6SF2 rs58542926 Polymorphism with Non-Alcoholic Fatty Liver Disease in Lean and Non-Lean Adults: A Case Control Study

Abstract

Introduction: Non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity and metabolic dysfunction but also occurs in lean individuals. Genetic variation in TM6SF2 may contribute to hepatic fat accumulation independently of body mass index. Aim: To assess the association of the TM6SF2 rs58542926 polymorphism with NAFLD and compare its distribution and clinical characteristics between lean and non-lean participants. Materials and Methods: This case-control study included 100 adults (50 cases and 50 controls) recruited at Era’s Lucknow Medical College and Hospital. Participants were classified as lean (BMI ≤22.9 kg/m²) or non-lean (BMI ≥23 kg/m²). TM6SF2 rs58542926 was genotyped using polymerase chain reaction-restriction fragment length polymorphism. Clinical, biochemical and anthropometric characteristics were compared using appropriate parametric or non-parametric tests, and categorical variables were compared using the Chi-square or Fisher’s exact test, as applicable. A p-value <0.05 was considered statistically significant. Results: The overall TM6SF2 genotype distribution differed significantly between cases and controls (p=0.007). The CT genotype was more frequent among cases than controls (44.0% versus 18.0%). Genotype distribution did not differ significantly between lean and non-lean participants. Lean cases had numerically higher high-density lipoprotein cholesterol and lower triglyceride concentrations and less severe ultrasonographic fatty liver than non-lean cases; however, these biochemical comparisons require interpretation with their corresponding measures of variability and p-values. Conclusion: The TM6SF2 rs58542926 genotype distribution differed between participants with and without NAFLD. However, no significant difference was demonstrated between lean and non-lean subgroups. Larger, adequately powered studies are required to determine whether BMI modifies this genetic association.

Keywords: Body Mass Index; Fatty Liver; Genetic Association Studies; Polymorphism, Single Nucleotide; TM6SF2 Protein, Human.