Association of genetic variations with NAFLD in lean individuals

Background & aims: How adiposity influences the effect of genetic variants on non-alcoholic fatty liver disease (NAFLD) in the Asian population remains unclear. We aimed to study the association between genetic risk variants and susceptibility/severity of NAFLD in the lean, overweight and obese individuals.

Methods: Nine hundred and four community subjects underwent proton-magnetic resonance spectroscopy and transient elastography examination. Lean (<23 kg/m² ), overweight (23-24.9 kg/m² ) and obesity (≥25 kg/m² ) were defined according to the body mass index cut-offs for Asians. NAFLD was defined as intrahepatic triglycerides ≥5%. PNPLA3, TM6SF2, MBOAT7 and 9 other gene polymorphisms were analysed by rhAMP^TM SNP assays.

Results: Five hundred and twenty-nine (58.5%), 162 (17.9%) and 213 (23.6%) subjects were lean, overweight and obese, respectively. The prevalence of NAFLD was 12.4%, 41.4% and 59.1% in the three groups (P < .001). Amongst those with NAFLD, lean subjects (30.3%) were more likely to carry the PNPLA3 rs738409 GG genotype than overweight (17.9%) and obese subjects (17.4%) (P = .003). Compared with the CC genotype, the GG genotype was associated with the greatest increase in the risk of NAFLD in lean subjects (odds ratio [OR] 6.04), compared with overweight (OR 3.43, 95% CI [1.06, 11.14]) and obese subjects (OR 2.51, 95% CI [0.93, 6.78]). Additionally, the TM6SF2 rs58542926 TT genotype was associated with reduced serum triglycerides only in lean subjects. A gene-BMI effect was not observed for the other gene polymorphisms.

Conclusions: The PNPLA3 rs738409 gene polymorphism has a greater effect on liver fat in Asian lean individuals than in overweight or obese ones.