title: Ala92 type 2 deiodinase allele increases risk for the development of hypertension.
abstract: 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.
authors.affiliation: Endocrinology, Diabetes, and Hypertension Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass 02115, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Gumieniak
authors.forename: Todd S
authors.initials: TS
authors.lastname: Perlstein
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Williams
authors.forename: Paul N
authors.initials: PN
authors.lastname: Hopkins
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Brown
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Raby
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Williams
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007453:Iodide Peroxidase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D007453:Iodide Peroxidase; D000097564:Iodothyronine Deiodinase Type II