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(Hypertension. 2007;49:461.)
© 2007 American Heart Association, Inc.

Original Articles

Ala92 Type 2 Deiodinase Allele Increases Risk for the Development of Hypertension

Olga Gumieniak; Todd S. Perlstein; Jonathan S. Williams; Paul N. Hopkins; Nancy J. Brown; Benjamin A. Raby; Gordon H. Williams

From the Endocrinology, Diabetes, and Hypertension Division (O.G., J.S.W., G.H.W.), Division of Cardiology (T.S.P.), and the Channing Laboratory (B.A.R.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass; Cardiovascular Genetics (P.N.H.), Cardiology Division, University of Utah, Salt Lake City; and the Department of Medicine (N.J.B.), Vanderbilt University, Nashville, Tenn.

Correspondence to Gordon H. Williams, Endocrinology, Diabetes, and Hypertension Division, 221 Longwood Ave, RFB-2, Boston, MA 02115. E-mail gwilliams{at}partners.org

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.

Key Words: hypertension • genetics • genetic predisposition to disease • thyroid hormones • iodothyronine deiodinase type 2

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