Stan Simona, Lambert Marie, Delvin Edgard, Paradis Gilles, O'loughlin Jennifer, Hanley James A, Levy Emile
Departments of Nutrition, Hôpital Sainte-Justine, Université de Montréal, Québec, Canada.
J Lipid Res. 2005 Feb;46(2):320-7. doi: 10.1194/jlr.M400346-JLR200. Epub 2004 Nov 16.
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.
越来越多的证据表明脂质异常与脂肪酸结合蛋白(FABP)和微粒体甘油三酯转运蛋白(MTP)基因变异之间存在关联。我们的目的是确定Ala54Thr FABP2和G-493T MTP基因多态性是否与青少年胰岛素抵抗综合征(IRS)风险增加相关,和/或改变伴随的血脂异常的表达。我们对1742名9岁、13岁和16岁的法裔加拿大人进行的研究没有提供证据表明FABP2或MTP基因型与IRS存在潜在易感性。然而,我们观察到FABP2对总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)和载脂蛋白B(apoB)浓度的影响因IRS状态而异(交互作用P值分别为0.045、0.018和0.017)。在IRS的代谢成分中,只有甘油三酯(TG)与FABP2基因多态性存在交互作用:与Thr/Ala和Ala/Ala相比,Thr/Thr基因型与TC、LDL-C和apoB随TG浓度的更陡峭升高相关(P<0.001)。IRS没有改变MTP基因多态性与任何生化参数之间的关联。我们的研究表明,FABP2等位基因变异对脂质特征的影响取决于背景,表明该变异在存在IRS或高甘油三酯血症的情况下可能在心血管发病机制中起重要作用。