Genome-wide association scan for survival on dialysis in African-Americans with type 2 diabetes

Abstract

Background: African-Americans (AAs) with diabetes have high incidence rates of end-stage renal disease (ESRD) with associated high mortality. Genetic factors modulating the risk of mortality on dialysis are poorly understood. Methods: A genome-wide association study was performed in 610 AAs with type 2 diabetes (T2D) and ESRD on dialysis, using the Affymetrix 6.0 platform (868,155 SNPs). Time to death was assessed using Cox proportional hazards model adjusting for ancestry and other confounding variables. Cases were censored at kidney transplant or (if living) at study conclusion. Results: Mean follow-up was 5.4 ± 3.5 years; 434 deaths were recorded. Five SNPs were associated with time to death at p < 1.00 × 10-6: rs2681019 (HR = 2.58, PREC = 8.00 × 10-8), rs815815 in CALM2 (HR = 1.51, PADD = 6.50 × 10-7), rs926392 (HR = 2.37, P REC = 4.80 × 10-7), and rs926391 (HR = 2.30, P REC = 7.30 × 10-7) near DHX35, and rs11128347 in PDZRN3 (HR = 0.57, PADD = 6.00 × 10-7). Other SNPs had nominal associations with time to death (p < 1.00 × 10 -5). Conclusion: Genetic variation may modify the risk of death on dialysis. SNPs in proximity to genes regulating vascular extracellular matrix, cardiac ventricular repolarization, and smoking cessation are associated with dialysis survival in AAs with T2D. These results warrant replication in other cohorts and races. Copyright © 2011 S. Karger AG, Basel.