Association of manganese superoxide dismutase and glutathione S-transferases genotypes with carotid atherosclerosis in patients with diabetes mellitus type 2.

Aim: The aim of the present study was to test the association between genetic polymorphisms with functional effects on redox regulation: Ala16Val of manganese superoxide dismutase (MnSOD or SOD2), polymorphic deletions of glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) and Ile105Val of the GSTP1 and carotid atherosclerosis in patients with type 2 diabetes.

Methods: The study enrolled 287 subjects with type 2 diabetes. Carotid atherosclerosis was quantified by ultrasonography as carotid intima-media thickness (CITM), plaque score from 0 to 6 and plaque type from 1 to 5. Genotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).

Results: The highest triglyceride level was observed in patients with MnSOD Val/Val genotype. Other polymorphisms did not show significant association with clinical parameters. We did not observe significant differences in MnSOD, GSTM1 and GSTP1 genotypes distribution according to CIMT, plaque type or plaque score. After adjustment for age, sex, smoking, BMI, lipid parameters and duration of hypertension and diabetes carriers of GSTT1-0 genotype showed an increased risk for higher plaque score (OR=2.29; p=0.012), but no association with CIMT and plaque stability was observed. Carrying of both GSTM1-0 and GSTT1-0 did not influence clinical parameters but increased risk for higher plaque score (OR=2.59; P=0.018).

Conclusion: We did not find a significant association between the MnSOD, GSTM1 and GSTP1 polymorphisms and carotid atherosclerosis. The GSTT1-0 genotype and GSTT1-0/GSTM1-0 haplotype might be a potential determinants of susceptibility to advanced atherosclerosis in patients with type 2 diabetes mellitus.