Identification of two polymorphisms in the promoter of the microsomal triglyceride transfer protein (MTP) gene: lack of association with lipoprotein profiles

The microsomal triglyceride transfer protein (MTP) catalyzes the transfer o f triglyceride, cholesteryl ester, and phosphatidylcholine between phosphol ipid surfaces. The 97-kD subunit imparts lipid transfer activity and thus p lays a role in the assembly of apolipoprotein B (apoB)-containing lipoprote ins. We tested whether polymorphisms in the promoter region of the large su bunit of the MTP gene might be related to different plasma lipid variables, atherosclerosis, and the risk of myocardial infarction (MI), We screened 8 38 bp in the promoter region of the MTP gene by PCR-SSCP and identified two polymorphisms at positions -400 (MTP/-400 (A-->t)) and -164 (MTP/-164 (T-- >c)), the latter being situated on a putative sterol responsive element (SR E) consensus sequence. The two polymorphisms, investigated in 622 male pati ents with hll and in 728 age-matched controls participating in the EC-TIM S tudy, were in nearly complete linkage disequilibrium (\D'\ = +0.98, less fr equent alleles being preferentially associated, P < 0.001), There were no s ignificant differences in genotype or allele frequencies between patients w ith MI and controls. Moreover, no significant associations between the two promoter polymorphisms and several lipid variables measured in the control groups of the ECTIM Study or coronary artery stenosis, angiographically ass essed in patients with MI, were detected. We conclude that these MTP polymo rphisms are unrelated to lipid variables or coronary heart disease in this study.