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 (Pinteraction = 0.013). In Whites, LPLGG homozygotes had greatest HDL-C at lower total, saturated, and monounsaturated fat intakes but lowest HDL-C at higher intakes of these fats (Pinteraction ≤ 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.