Additive Effects of the PPARγ, APOE, and FABP-2 Genes in Increasing Daylong Triglycerides of Normolipidemic Women to Concentrations Comparable to Those in Men

Background: Fasting and postprandial triglyceride (TG) concentrations vary considerably among individuals. TG metabolism is more efficient in women than in men, which may partly explain why females are protected against atherosclerosis. Our aim was to identify gender-specific genetic influences on fasting and postprandial TG concentrations under typical living conditions in healthy, lean, normolipidemic women. Methods: We studied 40 women and 48 men. Diurnal capillary TG profiles were calculated as the integrated area under the capillary TG curve averaged over 3 days. Genotypes of the FABP-2 , HL , LPL , APOE , and PPAR γ genes and the APOC-III , APOC-III/A-IV intergenic region were determined. Results: Three genes ( FABP-2 , APOE , and PPAR γ) had a significant additive effect only in women. Mean TG concentrations were fourfold higher in women carriers of the PPAR γ wild-type allele ( P = 0.044), threefold higher in carriers of the rare FABP-2 allele ( P = 0.006), and fivefold higher in carriers of the E2 allele of the APOE gene ( P = 0.037) than in noncarriers. None of these effects was observed in men. The presence of two or more of these adverse alleles increased TG concentrations in a dose-dependent manner. Women carriers of three adverse alleles had postprandial TG values comparable to those for men. Conclusions: An adverse combination of common alleles of the FABP-2 , APOE , and PPAR γ genes in women increases their TG concentrations to values comparable to those seen in men. Although this influence is not appreciable when studying fasting plasma TGs, it becomes apparent with use of a more sensitive index such as measurements made throughout the day.