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D2 Thr92Ala and PPARγ2 Pro12Ala Polymorphisms Interact in the Modulation of Insulin Resistance in Type 2 Diabetic Patients
Author(s) -
Estivalet Aline A.F.,
Leiria Leonardo B.,
Dora José M.,
Rheinheimer Jakeline,
Bouças Ana P.,
Maia Ana L.,
Crispim Daisy
Publication year - 2011
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1038/oby.2010.231
Subject(s) - medicine , insulin resistance , endocrinology , genotype , peroxisome proliferator activated receptor , allele , type 2 diabetes , deiodinase , type 2 diabetes mellitus , polymorphism (computer science) , insulin , diabetes mellitus , receptor , thyroid , biology , gene , genetics , triiodothyronine
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 assessment—IR (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 HOMA IR 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 HOMA IR index, with carriers of both D2 Ala/Ala genotype and PPARγ2 Ala12 allele showing the highest HOMA IR 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.