Abstract
Growing evidence suggests an association between lipid abnormalities and fatty acid binding protein (FABP) and microsomal triglyceride transfer protein (MTP) gene variants. Our objectives were to determine whether Ala54Thr FABP2 and G-493T MTP polymorphisms are associated with increased risks of insulin resistance syndrome (IRS) in youth and/or modify the expression of accompanying dyslipidemia. Our study of 1,742 French-Canadians aged 9, 13, and 16 years did not provide evidence of a potential predisposition to IRS related to either FABP2 or MTP genotypes. However, we observed a heterogeneity of the FABP2 effect by IRS status on total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), and apolipoprotein B (apoB) concentrations (P for interaction=0.045, 0.018, and 0.017, respectively). Among the metabolic components of IRS, only triglyceride (TG) displayed an interaction with FABP2 polymorphism: compared with Thr/Ala and Ala/Ala, the Thr/Thr genotype was associated with a steeper increase in TC, LDL-C, and apoB parallel to TG concentrations (P <0.001). IRS did not modify the associations between the MTP polymorphism and any of the biochemical parameters. Our study suggests that the effects of FABP2 allelic variations on lipid traits are context dependent, indicating that this variant may play an important role in cardiovascular pathogenesis in the presence of IRS or hypertriglyceridemia.
Highlights
Growing evidence suggests an association between lipid abnormalities and fatty acid binding protein (FABP) and microsomal triglyceride transfer protein (MTP) gene variants
There were no significant differences in FABP2 and MTP allele or genotype frequencies between subjects with and without insulin resistance syndrome (IRS) (Table 2)
An important new finding of this study is the demonstration of an interaction between FABP2 gene variants and IRS status in determining fasting plasma total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), and apolipoprotein B (apoB) concentrations
Summary
Growing evidence suggests an association between lipid abnormalities and fatty acid binding protein (FABP) and microsomal triglyceride transfer protein (MTP) gene variants. The association between the FABP2 gene variants and lipid disorders appears to be much more complex than hypothesized, because the same I-FABP mutation had no similar impact on the composition of plasma lipids, the basal metabolic rate, or insulin, glucose, and lipid levels in different populations [19]. The French-Canadian population, which is primarily and historically located in the province of Quebec, has the highest prevalence worldwide of lipoprotein lipase deficiency It includes a large pool of individuals at risk for atherosclerosis and other lipid-related diseases [22, 23]. These abnormalities are presumably related to a founder effect among the 8,000 ancestors of present-day French-Canadians, who have had relatively little cross-breeding with individuals from other national origin groups [24]
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