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The Ile148Met (rs738409, G-allele) in the patatin-like phospholipase domain-containing protein 3 gene ( PNPLA3 ) associates with liver fat content and may lead to loss-of-function (hydrolysis) or gain-of-function (CoA-dependent lysophosphatidic acid acyltransferase) defects. PNPLA3 is up-regulated by dietary carbohydrates, and interactions between rs738409 and carbohydrates, and sugar and ω6:ω3-polyunsaturated fatty acid (PUFA) ratio on hepatic fat accumulation have been reported. We examined interaction between rs738409 and overweight, and between rs738409 and dietary intakes (carbohydrates, sucrose and ω6:ω3-PUFA ratio), on fasting triglyceride levels. From the Malmo Diet and Cancer Study-Cardiovascular Cohort, 4,827 individuals without diabetes aged 58 ± 6 years, 2,346 with BMI ≤ 25 kg/m 2  and 2,478 with BMI > 25 kg/m 2 , were included in cross-sectional analyses. Dietary data were collected by a modified diet history method. Overweight modified the association between rs738409 and fasting triglyceride levels ( P   interaction  = 0.003). G-allele associated with lower triglycerides only among overweight individuals ( P  = 0.01). Nominally, significant interaction on triglyceride levels was observed between rs738409 and sucrose among normal-weight individuals ( P   interaction  = 0.03). G-allele associated with lower triglycerides among overweight individuals in the lowest tertiles of carbohydrate and ω6:ω3-PUFA ratio ( P  = 0.04 and  P  = 0.001) and with higher triglycerides among normal-weight individuals in the highest tertile of sucrose ( P  = 0.001). We conclude that overweight and dietary sucrose may modify the association between rs738409 and fasting triglyceride levels.   Electronic supplementary material  The online version of this article (doi:10.1007/s12263-014-0388-4) contains supplementary material, which is available to authorized users.

The PNPLA3 Ile148Met interacts with overweight and dietary intakes on fasting triglyceride levels