Accumulating evidence suggests that genes of the hypothalamic-pituitary-thyroid 
pathway influence susceptibility to hypertension. Type 2 iodothyronine 
deiodinase is responsible for the conversion of thyroxine to tri-iodothyronine 
for use in peripheral tissues. The present study evaluated whether a type 2 
iodothyronine deiodinase nonsynonymous polymorphism, threonine 92 to alanine 
(Thr92Ala), is a determinant of hypertension susceptibility. A total of 372 
euthyroid subjects were genotyped for Thr92Ala polymorphism using the Sequenom 
MassARRAY platform. Associations with hypertension and hypertension-related 
intermediate phenotypes were performed with generalized estimating equations. 
Type 2 iodothyronine deiodinase Thr92Ala allele frequencies differed 
significantly between hypertensive and normotensive subjects, with an excess of 
Ala92 carriers in hypertensive compared with normotensive subjects (64.8% versus 
47.1%; P=0.011). Adjusted for age, gender and race, the estimated odds ratio for 
hypertension in Ala92 allele carriers compared with Thr92 homozygotes was 2.11 
(95% CI: 1.15 to 3.89). Among euthyroid adults, the common Ala92 allele of the 
type 2 iodothyronine deiodinase increases risk for the development of 
hypertension. These data support an important role for genetic variation in the 
hypothalamic-pituitary-thyroid pathway in influencing susceptibility to 
hypertension.