Klotho G-395A Polymorphism as a Risk Factor for Atrial Fibrillation in Patients on Maintenance Hemodialysis

To explore the relationship between atrial fibrillation and the Klotho G-395A polymorphism in patients on maintenance hemodialysis (MHD).

The study included 120 MHD patients (persistent atrial fibrillation, n = 30; paroxysmal atrial fibrillation, n = 30; normal sinus rhythm, n = 60) and 120 control individuals. Klotho G-395A mutations were detected by the fluorescence quantitative polymerase chain reaction. ELISA was used to detect serum soluble Klotho (sKl) and intact fibroblast growth factor 23 (iFGF23) levels, and left atrium diameters were measured by echocardiography. Correlation analysis between Klotho G-395A genotypes, clinical parameters, and biochemical indexes was performed, along with logistic regression analysis to determine the risk factors for atrial fibrillation.

Three genotypes of Klotho G-395A, namely, GG, GA, and AA, were detected. The frequencies of the GA/AA genotypes and A allelic genes were significantly higher in the MHD patients than in the healthy controls, and these genotypes were associated with both atrial fibrillation and persistent atrial fibrillation. Furthermore, serum sKl, serum iFGF23, and left artery diameter were significantly associated with atrial fibrillation and also showed significant differences between the persistent and paroxysmal atrial fibrillation groups. The serum sKl level was negatively correlated with serum FGF23 level and the left atrium diameter, while the serum FGF23 level was positively correlated with the left atrium diameter. The incidence of atrial fibrillation and left atrium diameter was significantly higher in those with the GA/AA genotype than in those with the GG genotype, while the serum sKl levels were significantly lower. The GA/AA genotype was associated with a 5.444 times higher likelihood of atrial fibrillation than the GG genotype.

The A allele of Klotho G-395A may be a risk marker of atrial fibrillation in MHD patients. Moreover, sKl deficiency may contribute to the early development of atrial fibrillation in MHD patients.