Interactions between the -514C->T polymorphism of the hepatic lipase gene and lifestyle factors in relation to HDL concentrations among US diabetic men.

Low plasma HDL-cholesterol concentrations are a hallmark of diabetic dyslipidemia. A common polymorphism (-514C-->T) 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. 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. We followed men aged 40-75 y who participated in the Health Professionals Follow-Up Study in 1986. Among 18 159 men who returned blood samples by 1994, 780 had confirmed type 2 diabetes at blood drawing or during follow-up to 1998 and were free of cardiovascular disease at blood drawing. After adjustment for age, smoking, alcohol consumption, fasting status, glycated hemoglobin concentration, physical activity, and body mass index, HDL-cholesterol concentrations were significantly higher in men with the C/T or T/T genotype than in those with the C/C genotype (adjusted x: 40.9 and 38.8 mg/dL, respectively; P = 0.01). We observed significant LIPC -514 polymorphism x body mass index and LIPC -514 polymorphism x 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. Our study suggests that the effects of -514C-->T of the LIPC gene on HDL concentrations were modified by saturated fat intake and obesity.