Investigation the Impact of <i>KCNE1</i> -rs1805127 Polymorphism on Cardiac Patients with Atrial Fibrillation

<b><i>Objective:</i></b> This study aimed to investigate the association between the <i>KCNE1</i> single nucleotide polymorphism (SNP: rs1805127; T>C transition; S38G substitution) and atrial fibrillation (AF) in the Mazandaran population of northern Iran. <b><i>Materials and Methods:</i></b> 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 <i>KCNE1</i>-rs1805127 was performed using the restriction fragment length polymorphism method. The impact of <i>KCNE1</i>-rs1805127 on protein stability, function, and mRNA secondary structure was assessed using SIFT, I-Mutant, MetaRNN, and RNAsnp servers. <b><i>Results:</i></b> The results revealed a significant association of the CC genotype and C allele with AF (CC genotype: <i>p</i> value = 0.035; C allele: <i>p</i> value = 0.042). Furthermore, an association was observed between smoking (<i>p</i> value = 0.018), hypertension (<i>p</i> value = 0.046), and thyroid disorders (<i>p</i> value = 0.040) and AF. <i>in silico</i> predictions indicated that <i>KCNE1</i>-rs1805127 may impair protein function, reduce stability, and alter mRNA secondary structure. <b><i>Conclusions:</i></b> Based on the results obtained, <i>KCNE1</i>-rs1805127 may increase the risk of AF, particularly in the presence of risk factors such as smoking, hypertension, and thyroid disorders. Notably, <i>in silico</i> predictions from computational tools validate this observed impact. Given the role of the <i>KCNE1</i> gene in modulating ion channels and cardiac electrophysiology, we suggest that further research on <i>KCNE1</i> and its SNPs could provide valuable insights into its role in the pathogenesis of cardiac arrhythmias, particularly AF.