Abstract
Background: The physiological ratio of T3:T4 is essential to trigger the biological actions, since the T3:T4 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 T3:T4 and HDL3:HDL2 ratios and paraoxonase activity among Ala/Ala genotypes when compared with Thr/Thr + Thr/Ala genotypes. TSH and T4 levels were near to upper normal levels among Ala/Ala genotype. HDL3:HDL2 ratio is positively correlated with paraoxonase activity among Thr/Thr + Thr/Ala genotypes (r = 0.36, p 2:HDL2 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.
Highlights
The association of diabetes and thyroid dysfunction has long been known [1]
We propose that, Ala/Ala genotype with lower DIO2 levels would decrease relative concentration of T3 in situ could create a state of intracellular hypothyroidism, decreasing the expression of genes involved in energy, lipid metabolism and exacerbating the diabetic complications and leading to cardiovascular disease (CVD) risk
To the best of our knowledge, this is the first study intended to understand the association of DIO2 Thr92Ala SNP on thyroid function and the development of CVD risk among the South Indian type 2 diabetics
Summary
The association of diabetes and thyroid dysfunction has long been known [1]. The pervasiveness of thyroid dysfunction among the diabetics was mainly associated with autoimmune disease, female gender, obesity and insulin resistance. Lipids are one among the several biomolecules directly influenced by thyroid hormones (TH’s), thyroid dysfunction may contribute to alterations in quantity and quality of lipids, and it is defined as “dyslipidemia” This often occurs in diabetics [5] [6] and it exacerbates with thyroid dysfunction and leads to the development of cardiovascular disease (CVD) risk [7]. There is a significant decrease in T3:T4 and HDL3:HDL2 ratios and paraoxonase activity among Ala/Ala genotypes when compared with Thr/Thr + Thr/Ala genotypes. Conclusion: Phenotype expression of DIO2 gene, thyroid profile, HDL2:HDL2 ratio and paraoxonase activity are altered among the Ala/Ala genotype. Ala/Ala genotype plays a key role in thyroid dysfunction, dyslipidemia and the development of CVD risk among type 2 diabetics
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