The association of myeloperoxidase promoter polymorphism with carotid atherosclerosis is abolished in patients with type 2 diabetes.

OBJECTIVES

Type 2 diabetes mellitus (DM) enhances the development of atherosclerosis and reduces the activity of the oxidative myeloperoxidase (MPO) enzyme. MPO gene has a functional promoter polymorphism -463G/A which leads to high- (GG) and low-expression (AG, AA) genotypes.

DESIGN AND METHODS

We studied the association of MPO polymorphism with carotid artery intima-media thickness (IMT) in 198 randomly selected Finnish men of Caucasian origin, 161 non-diabetics and 37 with type 2 DM. Their carotid IMT was measured by high-resolution ultrasonography, and the overall mean IMT value was calculated. MPO genotypes were determined by the PCR-RFLP method.

RESULTS

We found significant MPO genotype-by-study-group (control/DM) interactions with the overall mean IMT and internal carotid IMT (p=0.05 and p=0.04, respectively). Among non-diabetic subjects, the overall carotid IMT was 7.3% higher in subjects with the low-activity genotype when compared to the high-activity (G/G) group. The results remained significant after adjustment for total cholesterol and smoking (p=0.015). No similar genotypic association was found for the subjects with type 2 DM.

CONCLUSIONS

This data suggests that in subjects with normal glucose metabolism, MPO gene variation may modify the carotid artery IMT.