Effects of the PNPLA3–SNP rs738409 on Serum Transaminase levels are modified by body mass index and alcohol consumption

For the common rs738409 C>G SNP, which is located in the patatin-like phospholipase domain-containing protein 3 (PNPLA3), a strong association between non-alcoholic fatty liver disease (NAFLD) has been detected [1], approved [2-8] and expanded to an association with liver-fat content in general [8-13] and serum transaminase levels [14]. Also an association to a higher risk of progression to cirrhosis in NAFLD patients has been shown [15]. Transaminase levels, particularly of alanine transaminase (ALT) and aspartate transaminase (AST), are strong indicators of hepatic steatosis [16] as well as of cardio-metabolic risks [17] and are associated with mortality even within their reference ranges [18]. Yet, a small number of studies reported gene-environment interactions for rs738409. Recently it has been shown that the G allele of rs738409 is associated with lower serum triglyceride and cholesterol levels and higher ALT levels in overweight individuals only [19]. Children with the minor G allele had more liver fat per unit omega-fat intake than major homozygous children [20]. In another study, sugar and carbohydrate intake in Hispanic children was positively related to hepatic fat fraction in GG carriers but not in CG and CC carriers [21].