The association of Klotho gene polymorphism with the mortality of patients on maintenance dialysis

Abstract

Despite medical progress, high morbidity and mortality rates have persisted in patients with end-stage renal disease (ESRD). The role in atherosclerosis and cardiovascular disease of klotho, an aging process-related gene, has been highlighted. Genetic variation in klotho has been reported to be a risk factor for coronary artery disease and ischemic stroke. Regarding the significance of cardiovascular disease for the outcome of ESRD patients, we investigated whether genetic variation of klotho was associated with mortality in ESRD patients on hemodialysis. 478 patients on maintenance hemodialysis for more than 3 months at dialysis facilities affiliated with the Western Dialysis Physician Association were enrolled in September 2004. Patient survival was checked annually until September 2007. Genotypings of klotho in terms of G395A in the promoter region, C1818T in exon 4, and KL-VS was performed. 45 deaths (11.2%) occurred over 3 years. Mortality was higher in the GA+AA group than in the GG group (18.9% vs. 6.7%, respectively, p < 0.001). Kaplan-Meier analysis also revealed that the survival of the GA+AA group was worse than that of GG group (p = 0.002). Cox's proportional hazards regression analysis showed that age, A allele carrier status in G395A of klotho, hemoglobin, albumin and HDL cholesterol levels were the significant factors affecting survival of hemodialysis patients. The A allele of the G395A polymorphism of klotho may be associated with the risk of mortality in Korean hemodialysis patients. Age, hemoglobin, albumin and HDL-C were also significant prognostic factors for survival in the present study.