Microsomal triglyceride transfer protein gene polymorphism strongly influences circulating malondialdehyde-modified low-density lipoprotein

Microsomal triglyceride transfer protein (MTP) plays a critical role in the assembly of lipoproteins. Therefore, we studied whether MTP gene polymorphisms are associated with atherosclerosis-promoting parameters, especially metabolic profiles and endothelial function, in healthy young men. One hundred one healthy men (mean age, 30.3 years) were studied. We analyzed the 2 promoter polymorphisms (−493G/T and −400A/T) of the MTP gene. Linkage disequilibrium analysis revealed a significant but incomplete linkage disequilibrium between the 2 polymorphisms (D' = 0.74). The −493T allele carriers (n = 26) showed marked increases in their levels of malondialdehyde-modified low-density lipoprotein (mean value, 135 vs 99 U/L in the G/G carriers; P = .003) and triglycerides (2.15 vs 1.16 mmol/L, P = .014), and reduced low-density lipoprotein particle size (259.2 vs 264.3 nm, P = .023), whereas there was no difference in apolipoproteins, insulin, adiponectin, homocysteine, folate, and endothelial function assessed using ultrasound measurement of brachial artery flow-mediated vasodilation. In contrast, the −400T allele carriers (n = 61) showed a reduced endothelial function (P = .044), accompanied by elevated apolipoprotein B levels in subjects with higher triglyceride levels. These results indicate that both promoter polymorphisms may be associated with the development of atherosclerosis and cardiovascular diseases, but that the mechanism responsible may be different.