D2 Thr92Ala and PPARγ2 pro12ala polymorphisms interact in the modulation of insulin resistance in type 2 diabetic patients

A A F Estivalet; L B Leiria; J M Dora; J Rheinheimer; A P Bouças; A L Maia; D Crispim

doi:10.1038/oby.2010.231

Back

D2 Thr92Ala and PPARγ2 pro12ala polymorphisms interact in the modulation of insulin resistance in type 2 diabetic patients

Journal article

Peer reviewed

D2 Thr92Ala and PPARγ2 pro12ala polymorphisms interact in the modulation of insulin resistance in type 2 diabetic patients

A A F Estivalet, L B Leiria, J M Dora, J Rheinheimer, A P Bouças, A L Maia and D Crispim

Obesity, Vol.19(4), pp.825-832

2011

DOI: https://doi.org/10.1038/oby.2010.231

Files and links (1)

url

https://doi.org/10.1038/oby.2010.231View

Published Version

Abstract

Type 2 deiodinase (D2) converts T4 into its active metabolite T3, an essential step in thyroid metabolism. A Thr92Ala polymorphism in the gene encoding D2 has been inconsistently associated with insulin resistance (IR). Recently, it was reported that the D2 Thr92Ala (rs225014) and the peroxisome proliferator-activated receptor (PPAR) γ2 Pro12Ala (rs1801282) polymorphisms interact in the modulation of metabolic syndrome in nondiabetic subjects. Here, we investigated the effect of both polymorphisms, isolated or in combination, on IR in patients with type 2 diabetes mellitus (DM2). The D2 Thr92Ala and PPARγ2 Pro12Ala polymorphisms were genotyped in 721 DM2 patients. IR was evaluated using the homeostasis model assessmentIR (HOMA IR) index in a subgroup of 246 DM2 subjects. The frequencies of D2 Ala92 and PPARγ2 Ala12 variants were 0.390 and 0.074, respectively. Patients carrying D2 Ala/Ala genotype had a higher fasting plasma insulin and HOMAIR index as compared to patients carrying Thr/Ala or Thr/Thr genotypes (P = 0.022 and P = 0.001, respectively). A significant synergistic effect was observed between D2 Thr92Ala and PPARγ2 Pro12Ala polymorphisms on HOMAIR index, with carriers of both D2 Ala/Ala genotype and PPARγ2 Ala12 allele showing the highest HOMAIR values, after adjusting for age, gender, BMI, and use of medication for DM2 (P = 0.010). In conclusion, DM2 patients harboring both D2 Ala/Ala genotype and PPARγ2 Ala12 allele seem to present more severe IR than those with other D2/PPARγ2 genotype combinations. These findings suggest that these polymorphisms interact in the IR modulation, which may constitute a potential therapeutic target.

Details

Title: D2 Thr92Ala and PPARγ2 pro12ala polymorphisms interact in the modulation of insulin resistance in type 2 diabetic patients
Authors: A A F Estivalet (Author) - Federal University of Rio Grande do Sul, Brazil
L B Leiria (Author) - Federal University of Rio Grande do Sul, Brazil
J M Dora (Author) - Federal University of Rio Grande do Sul, Brazil
J Rheinheimer (Author) - Federal University of Rio Grande do Sul, Brazil
A P Bouças (Author) - Federal University of Rio Grande do Sul, Brazil
A L Maia (Author) - Federal University of Rio Grande do Sul, Brazil
D Crispim (Author) - Federal University of Rio Grande do Sul, Brazil
Publication details: Obesity, Vol.19(4), pp.825-832
Publisher: Wiley-Blackwell Publishing Inc.
Date published: 2011
DOI: 10.1038/oby.2010.231
ISSN: 1930-7381
Organisation Unit: University of the Sunshine Coast, Queensland; Thompson Institute
Language: English
Record Identifier: 99451367602621
Output Type: Journal article

Metrics

68 Record Views

26 Times Cited - Web of Science

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types: Domestic collaboration
Web Of Science research areas: Endocrinology & Metabolism; Nutrition & Dietetics

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites