%0 Journal Article
%T Thr92Ala Polymorphism of Human Type 2 Deiodinase Gene (hD2) Affects the Development of Graves' Disease, Treatment Efficiency, and Rate of Remission
%A Babenko Alina
%A Popkova Daria
%A Freylihman Olga
%A Solncev Vladislav
%A Kostareva Anna
%A Grineva Elena
%J Journal of Immunology Research
%D 2012
%R 10.1155/2012/340542
%X Clinical symptoms vary in thyrotoxicosis, and severity of these depends on many factors. Over the last years, impact of genetic factors upon the development and clinical significance of thyrotoxic symptoms became evident. It is known that a production of T3 in various tissues is limited by deiodinase 2 (D2). Recent studies revealed that certain single nucleotide polymorphisms (including threonine (Thr) to alanine (Ala) replacement in D2 gene codon 92, D2 Thr92Ala) affect T3 levels in tissues and in serum. Individuals with Ala92Ala genotype have lower D2 activity in tissues, compared with that in individuals with other genotypes. In our study, we have assessed an association of D2 Thr92Ala polymorphism with (1) frequency of disease development, (2) severity of clinical symptoms of thyrotoxicosis, and (3) rate of remissions, in Graves' disease patients. 1. Introduction Over the last years, much attention has been paid to the emerging concept of a ¡°personalized therapy.¡± This recently developed approach, in particular, presumes using the information on patient¡¯s genotypes for the optimization of one¡¯s therapy. Analysis of genetic predisposition to sulfonylurea drug response in diabetes patients (Ser1369Ala variant in ABCC8 gene) serves as an example of the personalized therapy [1]. Ever increased introduction of genetic tests to the clinical laboratory promises developing a new therapeutic strategy¡ªthe personalized therapy of various diseases. In the current study, we have evaluated human type 2 deiodinase gene (hD2) polymorphism Thr92Ala as a potential genetic predictor of response to thyrostatic therapy in Graves¡¯ disease (GD). Deiodinases are the selenoenzymes regulating the transformation of thyroxin (T4) into triiodothyronine (T3) [2¨C4]. Type 1 deiodinase (D1) is expressed and synthesized in liver, kidney, and thyroid gland [2, 3] and is responsible for the levels of circulating T3 hormone [2¨C6]. Type 2 deiodinase (D2) enables T3 production in central nervous system, pituitary gland, brown adipose tissue, cardiac and skeletal muscle, and placenta [2¨C4]; it is expressed on lower levels in liver and kidney [2, 3]. Thus, D2 plays the key role in local tissue T3 production [6¨C11]. According to the published data, type 2 deiodinase activities increase manyfold in some tissues in Graves¡¯ disease patients [10]. Recent studies showed that polymorphisms of some deiodinase genes affect the production of thyroid hormones: human D2 gene, threonine (Thr) to alanine (Ala) replacement in codon 92 (D2 Thr92Ala) among them [2, 5, 12]. Ala92Ala homozygous subjects
%U http://www.hindawi.com/journals/jir/2012/340542/