An Association between MPO-463 G/A Polymorphism and Type 2 Diabetes

Abstract

Myeloperoxidase (MPO) is an enzyme which is a member of the haem-peroxidase superfamily and plays a role in production of reactive oxygen species. The most common polymorphism in the promoter region of MPO gene is -463 G/A. It was shown that carrying the GG genotype means increased activity of the gene approximately 2-3-fold compared to GA and AA genotypes. It was found that hyperglycaemia, modified oxidized proteins and increased advanced glycosylated end products (AGE) are related to oxidative stress in diabetes. Under the hyperglycaemic conditions, production of reactive oxygen radical is elevated in smooth muscle endothelial cells, mesengial and tubular endothelial cells. Especially, elevated lipid oxidation plays an important role in pathogenesis of diabetic complications such as cardiovascular complications. We examined the MPO -463 G/A polymorphism by using the PCR-RFLP method in 145 type 2 diabetic patients and 151 healthy controls. We observed that the AA genotype and A allele were protective variants against type 2 diabetes and the GG genotype was a risk factor for diabetes. While we studied the relationship between genotypes and biochemical parameters, we found that patients with the A allele had decreased serum cholesterol, triglyceride, VLDL levels and body mass index. We suggest that the MPO gene has an important role in pathogenesis of type 2 diabetes because of the increased frequency of GG genotype, which is related to increased activity and oxidant capacity of MPO in the patients.