Sex-specific association of fatty acid binding protein 2 and microsomal triacylglycerol transfer protein variants with response to dietary lipid changes in the 3-mo Medi-RIVAGE primary intervention study

Abstract

Background: The dietary guidelines targeted at reducing cardiovascular risk lead to largely heterogeneous responses in which genetic determinants are largely involved. Objectives: We evaluated the effect of fatty acid binding protein 2 (FABP2) Ala54Thr and microsomal triacylglycerol transfer protein (MTTP) −493G/T allelic variations on plasma lipid markers, at baseline and on the response to the 3-mo Medi-RIVAGE primary prevention study. Design: Subjects with moderate cardiovascular disease risk (n = 169) were advised to reduce total and saturated dietary fats and to increase intake of monounsaturated and polyunsaturated fats. They were genotyped for FABP2 Ala54Thr and MTTP −493G/T allelic variations, and plasma was processed for cardiovascular risk marker analyses. Results: At baseline, men and women homozygous for Thr54 presented a significant opposite profile for plasma oleic acid (18:1), triacylglycerol-rich lipoprotein (TRL) cholesterol, and TRL phospholipids. In addition, all Thr/Thr men presented higher 18:1 values than did women. For the MTTP −493G/T polymorphism, although all TT subjects presented high apolipoprotein B-48, a genotype × sex interaction was present for palmitic acid, linolenic acid, eicosatrienoic acid, and insulin. The prudent diet clearly improved plasma lipid markers. FABP2 genotype did not interact much with the amplitude of the response. However, for MTTP polymorphism, men homozygous for the T allele displayed a significantly more pronounced response than did men carrying the G allele, which is particularly evident by their larger decrease in the Framingham score. Conclusions: These 2 polymorphic loci are thus differently associated with the baseline lipid markers as well as with the response to nutritional recommendations, but both presented a marked sex-specific profile, with the response to diet being particularly efficient in men homozygous for the MTTP −493T allele.