Interactions between the 514C3T polymorphism of the hepatic lipase gene and lifestyle factors in relation to HDL concentrations

Background: Low plasma HDL-cholesterol concentrations are a hallmark of diabetic dyslipidemia. A common polymorphism (514C3T) of the hepatic lipase gene (LIPC), which accounts for up to 30% of the variation in hepatic lipase activity, has been associated with low hepatic lipase activity and high HDL-cholesterol concentrations. Objective: We examined the association between this polymorphism and plasma HDL-cholesterol concentrations and evaluated whether this association was modified by adiposity and dietary fat intake. Design: We followed men aged 40–75 y who participated in the HealthProfessionalsFollow-UpStudyin1986.Among18 159men who returned blood samples by 1994, 780 had confirmed type 2 diabetesatblooddrawingorduringfollow-upto1998andwerefree of cardiovascular disease at blood drawing. Results: After adjustment for age, smoking, alcohol consumption, fastingstatus,glycatedhemoglobinconcentration,physicalactivity, and body mass index, HDL-cholesterol concentrations were significantlyhigherinmenwiththeC/TorT/Tgenotypethaninthosewith the C/C genotype (adjusted x: 40.9 and 38.8 mg/dL, respectively; P 0.01). We observed significant LIPC 514 polymorphism body mass index and LIPC 514 polymorphism saturated fat intake interactions for HDL-cholesterol concentrations (P 0.003 for both). The T allele was associated with higher HDL-cholesterol concentrations only in men who were not overweight or who had higher saturated fat intake. Conclusion:Ourstudysuggeststhattheeffectsof514C3Tofthe LIPC gene on HDL concentrations were modified by saturated fat intake and obesity. Am J Clin Nutr 2005;81:1429–35.