Association of the type 2 deiodinase Thr92Ala polymorphism with type 2 diabetes: case-control study and meta-analysis.
OBJECTIVE
The type 2 deiodinase (D2) is a key enzyme for intracellular triiodothyronine (T(3)) generation. A single-nucleotide polymorphism in D2 (Thr92Ala) has been associated with increased insulin resistance in nondiabetic and type 2 diabetes (DM2) subjects. Our aim was to evaluate whether the D2 Thr92Ala polymorphism is associated with increased risk for DM2.


METHODS
A case-control study with 1057 DM2 and 516 nondiabetic subjects was performed. All participants underwent genotyping of the D2 Thr92Ala polymorphism. Additionally, systematic review and meta-analysis of the literature for genetic association studies of D2 Thr92Ala polymorphism and DM2 were performed in Medline, Embase, LiLacs, and SciELO, and major meeting databases using the terms 'rs225014' odds ratio (OR) 'thr92ala' OR 'T92A' OR 'dio2 a/g'.


RESULTS
In the case-control study, the frequencies of D2 Ala92Ala homozygous were 16.4% (n=173) versus 12.0% (n=62) in DM2 versus controls respectively resulting in an adjusted OR of 1.41 (95% confidence intervals (CI) 1.03-1.94, P=0.03). The literature search identified three studies that analyzed the association of the D2 Thr92Ala polymorphism with DM2, with the following effect estimates: Mentuccia (OR 1.40 (95% CI 0.78-2.51)), Grarup (OR 1.09 (95% CI 0.92-1.29)), and Maia (OR 1.22 (95% CI 0.78-1.92)). The pooled effect of the four studies resulted in an OR 1.18 (95% CI 1.03-1.36, P=0.02).


CONCLUSIONS
Our results indicate that in a case-control study, the homozygosity for D2 Thr92Ala polymorphism is associated with increased risk for DM2. These results were confirmed by a meta-analysis including 11 033 individuals, and support a role for intracellular T(3) concentration in skeletal muscle on DM2 pathogenesis.
Dora
José Miguel
JM
Thyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos 2350, 90035-003 Porto Alegre, RS, Brazil.
Machado
Walter Escouto
WE
Rheinheimer
Jakeline
J
Crispim
Daisy
D
Maia
Ana Luiza
AL
D000328:Adult; D000368:Aged; D000409:Alanine / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D006720:Homozygote; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016037:Single-Blind Method; D013912:Threonine / Q000235:genetics*; D000097564:Iodothyronine Deiodinase Type II
D000409:Alanine; D005819:Genetic Markers; D007453:Iodide Peroxidase; D013912:Threonine; D000097564:Iodothyronine Deiodinase Type II