Type II 5’Deiodinase Thr92Ala Polymorphism Is Associated with CVD Risk among Type 2 Diabetes Mellitus Patients

Abstract

Background: The physiological ratio of T 3 :T 4 is essential to trigger the biological actions, since the T 3 :T 4 ratio is efficiently regulated by extrathyroidal selenodeiodinases. Thr92Ala is a common variant in the DIO2 gene, which may have an implication in decreased phenotypic expression, but previous studies had conflicting outcomes. Consequently, we have undertaken this study to understand the effect of this SNP on CVD risk among type 2 diabetics. Methods: We included 130 T2DM patients without signs of CVD as controls and 106 proved CVD patients with T2DM as cases. The entire subjects were genotyped for Thr92Ala of DIO2 gene. FBG, lipid & thyroid profile, HDL sub-fractionations, type II deiodinase, malondialdehyde, paraoxonase, and superoxide dismutase were measured according to standard procedures. Results: The mean DIO2 levels in Ala/Ala genotypes were significantly lower than Thr/Thr + Thr/Ala genotypes (122 ± 39 ng/ml & 161 ± 32 ng/ml respectively). The thyroid profile was normal in all the subjects; merely it was altered significantly among the Ala/Ala genotypes when compared with Thr/Thr + Thr/Ala genotypes. Remarkably, there is a significant decrease in T 3 :T 4 and HDL 3 :HDL 2 ratios and paraoxonase activity among Ala/Ala genotypes when compared with Thr/Thr + Thr/Ala genotypes. TSH and T 4 levels were near to upper normal levels among Ala/Ala genotype. HDL 3 :HDL 2 ratio is positively correlated with paraoxonase activity among Thr/Thr + Thr/Ala genotypes (r = 0.36, p < 0.05). Conclusion: Phenotype expression of DIO2 gene, thyroid profile, HDL 2 :HDL 2 ratio and paraoxonase activity are altered among the Ala/Ala genotype. Thus, Ala/Ala genotype plays a key role in thyroid dysfunction, dyslipidemia and the development of CVD risk among type 2 diabetics.