Type 2 deiodinase Thr92Ala polymorphism impact on clinical course and myocardial remodeling in patients with Graves' disease

Abstract

Patients with thyreotoxicosis have variable clinical manifestations and various degree of cardiomyopathy which severity depends on many factors. Last years the genetic factors predicting development and clinical features of thyrotoxic symptoms and thyreotoxic cardiomyopathy became more evident. It is known, that production of T3 in various tissues including cardiac muscle is limited by deiodinase 2 (D2). Resent studies showed that certain polymorphisms, including Thr92Ala of D2 gene, are implicated in the development of thyrotoxic symptoms and thyreotoxic cardiomyopathy. Individuals with Ala92Ala genotype have lower D2 activity in tissues compared to other genotypes. In our study we focused on codon 92 polymorphism of D2 gene in relation to clinical manifestations of thyreotoxic cardiomyopathy and Echo-cardiography parameters in patients with Graves' disease.

GENETICS IN ENDOCRINOLOGY: Genetic variation in deiodinases: a systematic review of potential clinical effects in humans

“…The 92Ala allele may confer a decreased risk for thyrotoxicosis-related cardiomyopathy (i.e. left ventricle hypertrophy) in patients with Graves' disease, of which the authors proposed a potential protective effect of this genetic variant against hyperthyroidism-induced changes in heart tissue (33). Recently, Al-azzam et al (35) has detected an association between the D2-rs7140952 polymorphism with diastolic and systolic blood pressure in patients on thyroid hormone replacement therapy.…”

SNP Ser38Gly in the β-subunit of potassium channel gene KCNE1 and thyrotoxic cardiomyopathy in patients with Graves’ disease

“…При этом у лиц с эути-реоидным статусом, по данным литературы, была обнаружена связь полиморфизма Ser38Gly с разме-ром левого предсердия и конечным диастолическим размером левого желудочка [26]. Ранее нами были изучены влияния на развитие и течение ТКМП других полиморфизмов, ассоцииро-ванных с нетиреотоксической фибрилляцией пред-сердий, -Gly389Arg и Ser49Gly в гене β 1 -адренорецепторов, а также полиморфизма в гене дейодиназы 2-го типа Thr92Ala [6][7][8][9]. Результаты этих исследований не позволяют сделать вывод о на-личии ключевой роли генетических факторов в фор-мировании ТКМП.…”

“…В наших более ранних работах было продемон-стрировано влияние мутаций в генах дейодиназы 2-го типа и β1-адренорецепторов на течение ТКМП [6][7][8][9].…”

Thyrotoxic Cardiomyopathy

“…Therefore, this polymorphism is suggested to influence clinical manifestations and the severity of heart damage in patients with thyrotoxicosis. Our study shows that Thr92Ala D2 polymorphism can impact clinical course of Graves' disease and heart damage (Grineva et al, 2009). …”

“…Ala/Ala genotype of D2 polymorphism is also protective lowering total LVH risk and negative prognostic types of remodeling (concentric hypertrophy and dilatation of chambers), in particular. Therefore, medications leading to the decrease of deiodinase 2 activity could result in the reduced clinical manifestations of TCMP, however, no evidence is still available (Grineva et al, 2009). However, only high doses of propranolol (more than 160 mg daily) can significantly decrease T3 plasma level (for approximately 30%), and it can result in severe reduction of blood pressure in the majority of patients (normotensive ones) as far as only some of them develop systolic hypertension.…”