Impact of Gly389Arg 1-adrenoceptor polymorphism on the risk of chronic heart failure, the nature of its course, and on the efficiency of its treatment with carvedilol


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Abstract

Aim. To study в1-adrenoceptor gene (ADRB1) polymorphism on the development and course of chronic heart failure (CHF) and on the efficiency of its treatment with the в-adrenoblocker carvedilol in patients with coronary heart failure.
Subjects and methods. Two hundred and twenty-six patients (149 males and 77 females; mean age 55.9±5.8 years) with CHF, who received continuous basic therapy: angiotensin-converting enzyme inhibitors, a diuretic, an aldosterone antagonist, digoxin, and a в-adrenoblocker, were examined; 68 patients were given for 24 weeks carvedilol (its starting dose was 3.125 mg twice daily with its further adjustment until an individually tolerable dose was achieved). Genotypes were identified by the restriction fragment length polymorphism analysis of polymerase chain reaction products. A control group comprised 136 subjects (63 males and 73 females; mean age 55.9±5.8 years) without signs of cardiovascular disorders, as evidenced by the examination.
Results. In patients with CHF, the Gly allele of the Gly389Arg polymorphic locus of the ADRB1 gene in homozygous state was associated with the high individual risk for CHF, the severity of its clinical manifestations and the nature of its course while carriage of the Arg allele of the Gly39Arg polymorphic locus manifested itself as a protective factor. During long-term carvedilol therapy, CHF patients with the Arg/Arg genotype of the ADRB1 gene were observed to have a more pronounced decrease in the functional class of heart failure, a significant increase in left ventricular ejection, and a decrease in left ventricular end-systolic and end-diastolic sizes as compared with patients with the Gly/Arg genotype.
Conclusion. There were associations of the polymorphism of ADRB1 gene (the Gly39Arg polymorphic locus) with the development and severity of CHF and with the efficacy of therapy with в-adrenoblocker carvedilol.

About the authors

Aleksandr Trofimovich Teplyakov

Sergey Nikolaevich Shilov

Email: sergei@rnp.ru

Ekaterina Nikolaevna Berezikova

Yuliya Yur'evna Torim

Email: ytorim@list.ru

Anatoliy Vasil'evich Efremov

Email: eav48@yandex.ru

Igor' Dmitrievich Safronov

Email: safronov1962@mail.ru

S D Mayanskaya

Email: smayanskaya@mail.ru

Anna Aleksandrovna Popova

Email: ann24@ngs.ru

Elena Nikolaevna Voronina

Email: voronina_l@inbox.ru

Rostislav Sergeevich Karpov

A T Teplyakov

Research Institute of Cardiology, Siberian Branch, Russian Academy of Medical Sciences

Research Institute of Cardiology, Siberian Branch, Russian Academy of Medical Sciences

S N Shilov

Novosibirsk State Medical University

Novosibirsk State Medical University

E N Berezikova

Novosibirsk State Medical University

Novosibirsk State Medical University

Yu Yu Torim

Research Institute of Cardiology, Siberian Branch, Russian Academy of Medical Sciences

Research Institute of Cardiology, Siberian Branch, Russian Academy of Medical Sciences

A V Efremov

Novosibirsk State Medical University

Novosibirsk State Medical University

I D Safronov

Novosibirsk State Medical University

Novosibirsk State Medical University

S D Mayanskaya

Kazan State Medical Academy, Russian Agency for Health Care

Kazan State Medical Academy, Russian Agency for Health Care

A A Popova

Novosibirsk State Medical University

Novosibirsk State Medical University

E N Voronina

Novosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Novosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

R S Karpov

Research Institute of Cardiology, Siberian Branch, Russian Academy of Medical Sciences

Research Institute of Cardiology, Siberian Branch, Russian Academy of Medical Sciences

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