Additive effects of the PPARgamma, 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 PPARgamma genes and the APOC-III, APOC-III/A-IV intergenic region were determined.


RESULTS
Three genes (FABP-2, APOE, and PPARgamma) had a significant additive effect only in women. Mean TG concentrations were fourfold higher in women carriers of the PPARgamma 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 PPARgamma 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.
Ribalta
Josep
J
Facultat de Medicina, School of Medicine, Universitat Rovira i Virgili, Reus, Spain. josep.ribalta@urv.net
Halkes
Constantijn J M
CJ
Salazar
Juliana
J
Masana
Lluís
L
Cabezas
Manuel Castro
MC
D000328:Adult; D001057:Apolipoproteins E / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D005215:Fasting; D050556:Fatty Acid-Binding Proteins; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019518:Postprandial Period; D012737:Sex Factors; D014280:Triglycerides / Q000097:blood*
D001057:Apolipoproteins E; D002352:Carrier Proteins; C493404:FABP2 protein, human; D050556:Fatty Acid-Binding Proteins; D047495:PPAR gamma; D014280:Triglycerides