Associations between HDL-cholesterol and polymorphisms in hepatic lipase and lipoprotein lipase genes are modified by dietary fat intake in African American and White adults

Polymorphisms in genes involved in HDL-cholesterol (HDL-C) metabolism influence plasma HDL-C concentrations. We examined whether dietary fat intake modified relations between HDL-C and polymorphisms in hepatic lipase (LIPC-514C → T), cholesteryl ester transfer protein (CETP TaqIB), and lipoprotein lipase (LPL S447X) genes. Diet (food frequency questionnaire), plasma lipids, and LIPC, CETP, and LPL genotypes were assessed in ∼12,000 White and African American adults. In both races and all genotypes studied, minor allele homozygotes had highest HDL-C concentrations compared to the other genotypes (P < 0.001). However, main effects were modified by usual dietary fat intake. In African Americans - women somewhat more strongly than men - LIPC TT homozygotes with fat intake ≥33.2% of energy had ∼3-4 mg/dL higher HDL-C concentrations than CC and CT genotypes. In contrast, when fat intake was <33.2% of energy, TT homozygotes had HDL-C concentrations ∼3.5 mg/dL greater than those with the CC genotype but not different from those with the CT genotype (P_interaction = 0.013). In Whites, LPL GG homozygotes had greatest HDL-C at lower total, saturated, and monounsaturated fat intakes but lowest HDL-C at higher intakes of these fats (P_interaction ≤ 0.002). Dietary fat did not modify associations between CETP and HDL-C. In conclusion, these data show that plasma HDL-C differs according to LIPC, LPL, and CETP genotypes. In the case of LIPC and LPL, data suggest dietary fat modifies these relations.