Investigation the Impact of KCNE1-rs1805127 Polymorphism on Cardiac Patients with Atrial Fibrillation.

Abstract

Objective: This study aimed to investigate the association between the KCNE1 single nucleotide polymorphism (SNP: rs1805127; T>C transition; S38G substitution) and atrial fibrillation (AF) in the Mazandaran population of northern Iran. Materials and Methods: To conduct this case-control study, 120 blood samples from healthy individuals and 120 from individuals with AF were collected over an 11-month period. All participants underwent electrocardiogram analysis by a cardiologist. In addition, they completed a questionnaire that included questions about their medical history, lifestyle factors, and current medications. Genotyping of KCNE1-rs1805127 was performed using the restriction fragment length polymorphism method. The impact of KCNE1-rs1805127 on protein stability, function, and mRNA secondary structure was assessed using SIFT, I-Mutant, MetaRNN, and RNAsnp servers. Results: The results revealed a significant association of the CC genotype and C allele with AF (CC genotype: p value = 0.035; C allele: p value = 0.042). Furthermore, an association was observed between smoking (p value = 0.018), hypertension (p value = 0.046), and thyroid disorders (p value = 0.040) and AF. in silico predictions indicated that KCNE1-rs1805127 may impair protein function, reduce stability, and alter mRNA secondary structure. Conclusions: Based on the results obtained, KCNE1-rs1805127 may increase the risk of AF, particularly in the presence of risk factors such as smoking, hypertension, and thyroid disorders. Notably, in silico predictions from computational tools validate this observed impact. Given the role of the KCNE1 gene in modulating ion channels and cardiac electrophysiology, we suggest that further research on KCNE1 and its SNPs could provide valuable insights into its role in the pathogenesis of cardiac arrhythmias, particularly AF.