The MTP-493TT genotype is associated with peripheral arterial disease: Results from the Linz Peripheral Arterial Disease (LIPAD) Study

Objectives: Microsomal triglyceride transfer protein (MTP) transfers lipids into apoprotein B-containing lipoproteins for secretion from liver, intestine, and heart. We hypothesized the -493T single nucleotide polymorphism in the MTP promoter region to be associated with altered lipoprotein levels and with presence of peripheral arterial disease (PAD). Design and methods: 433 patients with symptomatic PAD and 433 controls matched for sex and age from the Linz Peripheral Arterial Disease (LIPAD) study were genotyped cross-sectionally for the -493T single nucleotide polymorphism in the promoter region of the MTP gene. Results: The frequency of the -493T allele in patients with PAD was 0.320, whereas it was 0.255 in controls (p < 0.001). The MTP -493TT genotype was independently associated with PAD, even after adjustment for LDL cholesterol. The odds ratio of the -493TT MTP genotype for PAD was 3.18 (95% CI, 1.76-5.71) when adjusted for current smoking, arterial hypertension, LDL cholesterol, triglycerides, glycohemoglobin, C-reactive protein, and homocysteine. Furthermore, we found an association between the MTP promoter polymorphism and the apolipoprotein B-containing lipoproteins total-cholesterol (p = 0.011), LDL cholesterol (p = 0.002) and apolipoprotein B (P = 0.034). Conclusions: Our results provide preliminary evidence for a potential role of the NITP -493TT genotype in the pathogenesis of PAD. (c) 2008 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.