PT - JOURNAL ARTICLE
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DP - 2020-12-11
4100 - 10.1016/S0735-1097(19)31009-5
SO - https://repo.bashgmu.ru/publication/912
AB - Background
Sick sinus syndrome (SSS) can result from genetic and environmental factors. More than a dozen genetic loci are under investigations.

Objective
To investigate whether 5 connective tissue and 5 ion channel gens involved in the pathogenesis of non-familial SSS.

Methods
In the case-control study, DNA was isolated from peripheral blood of 284 unrelated SSS patients (65.65±11.0 years) and 243 healthy donors (62.56±14.05). 10 single nucleotide polymorphisms (SNPs) were genotyped by the real-time polymerase chain reaction. Logistic regression was used to detect the association of SNPs with SSS in different models.

Results
In the control group Hardy-Weinberg equilibrium was PH-W=0.022 for CHRM2 (rs2350782), PH-W=0.081 for SYT10 (rs7980799), PH-W=0.18 for MYH6 (rs365990), PH-W=0.37 for FNDC3B (rs9647379), PH-W=0.23 for MIR146A (rs2910164), PH-W=0.0001 for MIR196A2 (rs11614913). No statistically significant differences were observed in the CHRM2 rs2350782 frequency distribution (χ2=2.46, P=0.118 for alleles and χ2=3.41, P=0.18 for genotypes). Genotypes of the dominant model (T/T+T/C) were more common in the control group (36.2%) compared with SSS patients (28.9%) Padj=0.052. Analysis, depending on the type of SSS, showed FNDC3B rs9647379 C/C genotype was associated with bradycardia (P=0.05, OR=1.55). The protective effect was shown for the additive model FNDC3B rs9647379 in (P=0.014, OR=0.71). In ion channel in the control group PH-W=0.0001 was for HCN4 (rs7164883), PH-W=0.49 for SCN10A (rs6795970), PH-W=0.069 for KCNE1 (rs1805127), PH-W=1.0 for CLCNKA (rs10927887), PH-W=0.0001 for KCNN3 (rs13376333). KCNE1 rs1805127 was of statistical significance (χ2 = 8.40, P = 0.02), so the T/T genotype was more frequent in the control group, 15.64% vs. 8.45% in the SSS, OR = 0.50, 95% CI (0.29-0.86).

Conclusion
FNDC3B rs9647379, CHRM2 rs2350782 of connective tissue; T/T genotype of the KCNE1 rs1805127 and CLCNKA g.16351275A>G of ion channel genes may be risk factors for the non-familia SSS.