Association of <em>KCNH2</em> Gene Expression with Atrial Fibrillation in an African Population

Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with an increased risk of stroke and heart failure, with both genetic and environmental factors contributing to its pathophysiology. Emerging evidence suggests that KCNH2 gene dysregulation may play a role in arrhythmogenesis, yet data in African populations remain limited. This study investigated KCNH2 gene expression in AF patients and its association with clinical and laboratory parameters. In a matched case–control design at Aminu Kano Teaching Hospital, Nigeria, 25 participants (14 AF patients and 11 age-matched controls) were enrolled. Peripheral blood was collected for RNA extraction and lipid profiling. KCNH2 expression was quantified using reverse transcription real-time PCR, and relative fold changes were calculated via the 2^−ΔΔCt method. Compared with controls, AF patients exhibited significantly higher total cholesterol, LDL cholesterol, and triglyceride levels (p ≤ 0.029). KCNH2 expression was markedly reduced in AF patients, with a 17-fold decrease (median 0.12, IQR 0.04–0.71) versus controls (2.06, IQR 1.30–2.85; p &lt; 0.001). QTc intervals were significantly prolonged in AF patients, and serum triglycerides were negatively correlated with KCNH2 expression (r = –0.472, p = 0.003). These findings suggest that downregulation of KCNH2, in combination with lipid abnormalities and QTc prolongation, may contribute to AF pathogenesis, highlighting the potential utility of molecular and metabolic profiling in risk assessment and precision management of AF.