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Genetic aspects of sick sinus syndrome
Authors: Chernova A.A., Nikulina S.Yu., Tret’yakova S.S., Voyevoda M.I., Maksimov V.N., Chernov V.N.
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Aim. To study the association between polymorphic allelic variants of the alpha-2В-adrenoreceptor gene (ADRA2B), endothelial nitric oxide synthase gene (NOS3), connexin protein gene 40 (Cx40), cardiac myosin heavy chain gene (MYH6), and voltage-gated sodium channels gene (SCN5A) and development of the idiopathic sick sinus syndrome. Methods. 14 probands with primary symptoms of sick sinus syndrome and their 110 relatives of the I–III degree kinship were examined. At the Berzon City Clinical Hospital 20 all participants underwent a clinical and instrumental examonation that entailed the clinical examination, electrocardiography, atropine test, echocardioscopy, bicycle ergometry, left atrial transesophageal pacing, 24-hour ECG (holter) monitoring. In addition, all the examined people underwent molecular genetic analysis of polymorphic allelic variants ADRA2B, NOS3, Cx40, MYH6, SCN5A using PCR in Novosibirsk Scientific Research Institute of Cytology and Genetics. The data was statistically processed on an IBM PC using the Statistica 7.0 software package. Results. Homozygous genotype in a rarer DD allele ADRA2B gene was found to dominate in sick sinus syndrome patients (28 %) compared to participants in the control group (8.99 %). Heterozygous genotype of the 4a/4b gene NOS3 was found to significantly dominate in sick sinus syndrome patients (41.18 %) compared to participants in the control group (25.39 %). Heterozygous genotype 44G >A of the Cx40 gene was found to significantly prevail in sick sinus syndrome (45.07 %) compared to participants in the control group (29.44 %). None of the investigated samples revealed polymorphism 2161C > T (Arg721Trp) of MYH6 gene. Homozygous genotype in rarer allele of (GG) gene SCN5A was found to prevail in primary sick sinus syndrome patients (4.29 %) compared to the absence of this genotype in the control group (0 %). The distribution of ADRA2B, NOS3, Cx40, SCN5A gene genotype in patients with latent sick sinus syndrome was proved to be consistent with that of the genotypes of the above genes in the general population of primary sick sinus syndrome patients. The allelic variants of the above genes were not found to be associated with ompensated sick sinus syndrome. Conclusion. The genetic predictors of idiopathic sick sinus syndrome are heterozygous genotypes 44 GA and 4a/4b genes Cx 40 and NOS3 as well as homozygous genotypes in rare allele DD and GG genes ADRA2B and SCN5A. Polymorphic allelic variant 2161C > T (Arg721Trp) of MYH6 gene was not revealed in the examined cohort of Krasnoyarsk population. The distribution of the genotypes of the investigated genes in latent sick sinus syndrome patients was found to be consistent with that of the genotypes in the general population of primary sick sinus syndrome patients.