The rs225017 Polymorphism in the 3′UTR of the Human DIO2 Gene Is Associated with Increased Insulin Resistance

Abstract

The Thr92Ala (rs225014) polymorphism in the type 2 deiodinase (DIO2) gene has been associated with insulin resistance (IR) and decreased enzyme activity in human tissues but kinetic studies failed to detect changes in the mutant enzyme, suggesting that this variant might be a marker of abnormal DIO2 expression. Thus, we aimed to investigate whether other DIO2 polymorphisms, individually or in combination with the Thr92Ala, may contribute to IR. The entire coding-region of DIO2 gene was sequenced in 12 patients with type 2 diabetes mellitus (T2DM). Potentially informative variants were evaluated in 1077 T2DM patients and 516 nondiabetic subjects. IR was evaluated using the homeostasis model assessment (HOMA-IR) index. DIO2 gene sequencing revealed no new mutation but 5 previously described single nucleotide polymorphisms (SNPs). We observed that all T2DM patients displaying high HOMA-IR index (n = 6) were homozygous for the rs225017 (T/A) polymorphism. Further analysis showed that the median fasting plasma insulin and HOMA-IR of T2DM patients carrying the T/T genotype were higher than in patients carrying the A allele (P = 0.013 and P = 0.002, respectively). These associations were magnified in the presence of the Ala92Ala genotype of the Thr92Ala polymorphism. Moreover, the rs225017 and the Thr92Ala polymorphisms were in partial linkage disequilibrium (|D′| = 0.811; r 2 = 0.365). In conclusion, the rs225017 polymorphism is associated with greater IR in T2DM and it seems to interact with the Thr92Ala polymorphism in the modulation of IR.

Correlation between Insulin Resistance and Thyroid Nodule in Type 2 Diabetes Mellitus

“…TNF can also impact 5′-deiodinase to reduce T4 convert to T3. Genetic abnormalities are shown to damage the expression and activity of type 2 deiodinase that has been associated with increased IR [ 34 ]. The activity of type 1 deiodinase may also be related to IR.…”

A novel polymorphism in protein kinase AMP‐activated catalytic subunit alpha 2 (PRKAA2) is associated with type 2 diabetes in the Han Chinese population

“…To determine whether the candidate polymorphism was independently associated with T2DM, multiple logistic regression analysis was performed with T2DM as the dependent variable and age, sex, BMI, and genotype information for the SNPs as independent variables . Haplotype interaction between the rs2746342 and rs2143754 polymorphisms in modulating FPG was tested by general linear model (GLM) univariate analyses after adjusting for covariates (age, sex, BMI) . All analyses were performed using the Stata/SE version 12.0 (Stata Corp., College Station, TX, USA) and SPSS version 18.0 (SPSS, Chicago, IL, USA).…”

“…19 Haplotype interaction between the rs2746342 and rs2143754 polymorphisms in modulating FPG was tested by general linear model (GLM) univariate analyses after adjusting for covariates (age, sex, BMI). 20 All analyses were performed using the Stata/SE version 12.0 (Stata Corp., College Station, TX, USA) and SPSS version 18.0 (SPSS, Chicago, IL, USA). Two-sided P < 0.05 was considered significant.…”

TSHβX1 Splice Variant Expression and D2 Thr92Ala Polymorphism Analysis in Pregnant Women with Thyroid Diseases

“…For instance, DIO2 and TSH have been implicated in the thyroid disease development. Polymorphisms in DIO2 could interfere in the expression level or the activity of this enzyme, potentially altering the metabolism of thyroid hormones [7,21]. On this field, comparing the Thr92Thr homozygous and Thr92Ala heterozygous genotypes, the D2 activity has been found to decline among Ala92Ala homozygous [22].…”