PNPLA3 gene polymorphism accounts for fatty liver in community subjects without metabolic syndrome

Summary Background The rs738409 GG variant in patatin‐like phospholipase 3 ( PNPLA 3 ) is associated with non‐alcoholic fatty liver disease ( NAFLD ) and disease severity. However, it remains unclear if it contributes to the development of NAFLD through affecting dietary pattern. Aim To examine the association among PNPLA 3 gene polymorphism, dietary pattern, metabolic factors and NAFLD . Methods Liver fat and fibrosis were assessed by proton‐magnetic resonance spectroscopy and transient elastography in 920 subjects from a population screening project (251 had NAFLD ). Dietary nutrient intake was recorded using a locally validated food‐frequency questionnaire. Results The prevalence of GG genotype in NAFLD subjects was 20.7%, compared to 10.6% in controls ( P < 0.001). Macronutrient intake was similar among subjects with different PNPLA 3 genotypes. The presence of G allele was a predictor of NAFLD independent of nutrient intake and other metabolic factors (adjusted odds ratio to CC : CG , 2.00; GG , 2.68). In subjects without metabolic syndrome, G allele was even more closely correlated with NAFLD diagnosis (adjusted odds ratio to CC : CG , 2.22; GG , 3.39). The prevalence of NAFLD was only 12% in subjects with CC genotype and no metabolic syndrome, and increased to 34% in those with GG genotype and no metabolic syndrome. While NAFLD subjects had significantly lower fibre intake, there was no significant interaction between PNPLA 3 and dietary pattern. Conclusions The G allele in PNPLA 3 rs738409 increases the risk of NAFLD in the general population, especially in subjects without metabolic syndrome, independent of dietary pattern and metabolic factors.