Absence of association between genetic variation in the promoter of the microsomal triglyceride transfer protein gene and plasma lipoproteins in the Framingham Offspring Study

Microsomal triglyceride transfer protein (MTP) is a lipid transfer protein that is required for the assembly and secretion of very low density lipopro teins (VLDL) by the liver and chylomicrons by the intestine. The common G-4 93T polymorphism of the MTP promoter has been shown to be associated with d ecreased plasma LDL-cholesterol and ApoB content of VLDL. The purpose of th e present study was, therefore, to investigate the association of this muta tion with variations in lipid and apoprotein levels, lipoprotein subclass p rofiles and coronary heart diasease (CHD) risk in a population-based sample of 1226 male and 1284 female Framingham Offspring participants. In men and women, no significant association was found between the G-493T MTP polymor phism and variations of plasma levels of total cholesterol, LDL-cholesterol , apoprotein B, HDL-cholesterol, apoprotein AI and triglycerides. In order to further investigate potential relationships with variations of lipoprote in phenotypes, lipoprotein subclass profiles were measured using automated nuclear magnetic resonance (NMR) spectroscopy. Each NMR profile yielded inf ormation on lipid mass of VLDL, LDL, and HDL subclasses. In both genders, t here was no significant association between the G-493T polymorphism and var iability of lipoprotein subclass distributions or lipoprotein particle size . Furthermore, no significant association was found between the polymorphis m of the MTP promoter and prevalence or the age of onset of CHD. Thus, our results suggest that the G-493T mutation in the MTP promoter is unlikely to have significant implications for cardiovascular disease in men and women. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.