Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is a burgeoning health problem worldwide. Genetic predisposition increases susceptibility to NAFLD. The PNPLA3 rs738409 and TM6SF2 rs58542926 polymorphisms are genetic risk factors for NAFLD. Objectives: This study aimed to investigate the association of rs738409 and rs58542926 polymorphisms with NAFLD among the Iranian population in two groups: (1) Population-based NAFLD (PB-NAFLD), and (2) clinic-based NAFLD (CB-NAFLD). Methods: This case-control study included a group of healthy individuals without NAFLD as the control group and two case groups, PB-NAFLD and CB-NAFLD. All individuals underwent clinical and laboratory assessments and were also diagnosed using ultrasonography. Genotyping for rs738409 and rs58542926 polymorphisms was carried out by the PCR-RFLP method. Results: A total of 110 control, 108 PB-NAFLD, and 73 CB-NAFLD individuals were included in the study. The distribution of rs738409 GG+CG in the PB-NAFLD was 39.8% while it was 52.7% in the control group (P = 0.06, OR = 0.59). The distribution of rs738409 GG in the CB-NAFLD was 19.2%, while it was 8.2% in the control group (P = 0.04, OR = 2.66). The distribution of rs58542926 genotypes was not significantly different between the NAFLD and control groups. In multivariate analysis, metabolic syndrome (OR = 2.85) and BMI > 25 (OR = 3.32) were independent determinants of NAFLD in the PB-NAFLD group, and BMI > 25 (OR = 7.15) was an independent determinant of NAFLD in the CB-NAFLD group. Conclusions: In this study, the PNPLA3 rs738409 polymorphism was associated with NAFLD in the CB-NAFLD cohort; however, the same was not observed for the PB-NAFLD cohort. The TM6SF2 rs58542926 polymorphism was not associated with NAFLD in the Iranian population.

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