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Вклад распространенных однонуклеотидных полиморфизмов гена β1-адренорецептора в изменения, происходящие в сердечно-сосудистой системе при тиреотоксикозе

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Выявление структуры генетической компоненты распространенных болезней является одним из ключевых направлений в современной медицине. При тиреотоксикозе (ТТ) наиболее актуальны предикторы, определяющие вероятность развития ремиссии заболевания и риск сердечно-сосудистых осложнений. Мы сосредоточились именно на втором из обозначенных аспектов. Кандидатами для изучения являются прежде всего те гены, экспрессия которых, с одной стороны, регулируется трийодтиронином и которые, с другой стороны, играют ключевую роль в изменении сократимости миокарда и аритмогенезе. Сюда относятся, в частности, полиморфизмы гена ?1-адренорецептора (?1-АР): полиморфизм в кодоне 389 (Gly389Arg) и полиморфизм в кодоне 49 (Ser49Gly). Целью настоящей работы явилось изучение влияния полиморфизмов гена ?1-АР на клинические и эхокардиографические показатели при тиреотоксикозе и их динамику в процессе лечения. Было обследовано 165 пациентов с болезнью Грейвса и явным ТТ без сопутствующей патологии сердца. Анализ полученных данных показал, что полиморфизмы гена ?1-АР оказывают умеренное влияние на характер ремоделирования левого желудочка, определяя в некоторой степени риск гипертрофии левого желудочка и ее характер (эксцентрическая, концентрическая), а также риск развития предсердных нарушений ритма. Обнаружена тенденция к наименьшему риску развития сердечно-сосудистых осложнений ТТ у носителей комбинации генотипа GG по полиморфизму Ser49Gly и генотипа СС по полиморфизму Gly389Arg. Однако статистически достоверных эффектов данных полиморфизмов выявлено не было.

Ключевые слова:
полиморфизм β1-адренорецептора Gly389Arg, полиморфизм β1-адренорецептора Ser49Gly, тиреотоксикоз, эхокардиография, гипертрофия левого желудочка, фибрилляция предсердий, Gly389Arg polymorphism of β1-adrenoreceptor, Ser49Gly polymorphism of β1-adrenoreceptor, thyrotoxicosis, Echo-CG, left ventricular hypertrophy, atrial fibrillation

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The Contribution of the Common Single-nucleotide Polymorphisms of β1-Adrenoreceptor Gene to Cardiovascular Alteration in Patients with Thyrotoxicosis

The detection of a genetic organization of common diseases is one of the first key direction in modern medicine. In thyrotoxicosis, identification of genetic predictors, defining remission and the risk of cardiovascular complications is of a great importance. We gave attention to the second of above mentioned aspects. Candidates for genetic prediction are the genes regulated by triiodothyronine and playing a key role in changing of the myocardial contractility and arrhythmogenesis. There are SNPs of the ?1-adrenergic receptor (ADRB1) gene among them: polymorphism in the 389 codon (Gly389Arg) and polymorphism in codon 49 (Ser49Gly). The investigation goal was to determine whether the deleterious effects on cardiovascular system of the thyroid hormones excess in people with thyrothoxicosis were modified by polymorphic variants of ADRB1 gene. So we investigated the possible link of these two SNPs with clinicopathologic findings, echocardiographic parameters and the changes during therapy in 165 patients with a thyrotoxicosis caused by Gravesdisease without any nonthyrotoxic cardiovascular disorders. The data analysis demonstrates that both Gly389Arg and Ser49Gly polymorphisms have very moderate influence on the risk of atrial arrhythmias, left ventricular hypertrophy and its type (concentric or eccentric). Genotype Gly389Gly (Gly389Arg polymorphism) or genotype Gly49Gly (Ser49Gly polymorphism) carriers have tendency to the lowest risk of cardiovascular complications during thyrohoxicosis, but no statistically significant effects were revealed.

Keywords:
полиморфизм β1-адренорецептора Gly389Arg, полиморфизм β1-адренорецептора Ser49Gly, тиреотоксикоз, эхокардиография, гипертрофия левого желудочка, фибрилляция предсердий, Gly389Arg polymorphism of β1-adrenoreceptor, Ser49Gly polymorphism of β1-adrenoreceptor, thyrotoxicosis, Echo-CG, left ventricular hypertrophy, atrial fibrillation