Correlation between HCN4 gene polymorphisms and lone atrial fibrillation risk

Area of Science:

• Cardiovascular Genetics
• Electrophysiology

Background:

• Atrial electrical remodeling (AER) is a key factor in the development of atrial fibrillation (AF).
• The hyperpolarization activated cyclic nucleotide gated potassium channel 4 (HCN4) gene is implicated in AER and may influence AF susceptibility.

Purpose of the Study:

• To investigate the association between specific HCN4 gene polymorphisms (rs498005 and rs7164883) and the risk of lone AF in a Chinese Han population.
• To explore the correlation of these HCN4 polymorphisms with clinical features of AF, including atrial late potentials.

Main Methods:

• A case-control study design was employed.
• Sanger sequencing was used for genotyping HCN4 polymorphisms (rs498005 and rs7164883).
• Statistical analyses included chi-squared tests, odds ratios with 95% confidence intervals, logistic regression, and Mann-Whitney U tests with Bonferroni correction.

Main Results:

• The C allele of rs498005 was significantly associated with an increased risk of AF (OR=1.412), even after adjusting for clinical factors (adjusted OR=1.473).
• The G allele of rs7164883 showed a marginal association with enhanced AF risk after adjustment (adjusted OR=1.742).
• HCN4 rs498005 genotype was significantly correlated with atrial late potential parameters (TP and LP20).

Conclusions:

• HCN4 gene polymorphisms rs498005 and rs7164883 are significantly associated with an increased risk of atrial fibrillation.
• These findings suggest that HCN4 gene variations play a role in the pathogenesis of AF, potentially through effects on atrial electrical remodeling.