Correlation between HCN4 gene polymorphisms and lone atrial fibrillation risk.

Background and objective: Atrial electrical remodelling (AER) was significantly associated with atrial fibrillation (AF) development. Polymorphisms in hyperpolarization activated cyclic nucleotide gated potassium channel 4 (HCN4) gene might be correlated with AER. In the present study, we explored the association of HCN4 polymorphisms (rs498005 and rs7164883) with lone AF risk in a Chinese Han population. Methods: In this case-control study, the Sanger sequencing method was utilized to genotype the HCN4 polymorphisms. Relative risk of AF was assessed by the χ² test, and presented by odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Logistic regression analysis was performed for multivariate analysis. The effects of HCN4 polymorphisms on AF clinical features were analyzed by the Mann-Whitney U test and adjusted by the Bonferroni method. Results: C allele of rs498005 was significantly correlated with increased risk of AF (OR = 1.412, 95%CI = 1.012-1.970), and the association still exited after adjustment by age, gender, the status of smoking and drinking, histories of diabetes, hyperlipidaemia and myocardial infarction (adjusted OR = 1.473, 95%CI = 1.043-2.081). G allele of rs7164883 SNP was marginally associated with enhanced AF risk after adjustment by the above clinical parameters (adjusted OR = 1.742, 95%CI = 1.019-2.980). Atrial late potential (ALP), including TP (P wave duration after filtering) and LP₂₀ (the amplitude of superimposed potential in the final 20 ms of P wave) were significantly associated with rs498005 genotype (p < .001). Conclusion: HCN4 rs498005 and rs7164883 polymorphisms are significantly associated with AF risk.

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