Genetic variation in APOL1 associates with younger age at hemodialysis initiation

Abstract

African Americans have a markedly higher incidence of ESRD compared with other racial groups. Two variants in the APOL1 gene, to date observed only among individuals of recent African ancestry, associate with increased risk for renal disease among African Americans. Here, we investigated whether these risk alleles also associate with age at initiation of chronic hemodialysis. We performed a cross-sectional study of 407 nondiabetic African Americans with ESRD who participated in the Accelerated Mortality on Renal Replacement (ArMORR) study, a prospective cohort of incident chronic hemodialysis patients. African Americans carrying two copies of the G1 risk allele initiated chronic hemodialysis at a mean age of 49.0 ± 14.9 years, which was significantly younger than both subjects with one copy of the G1 allele (55.9 ± 16.7 years; P = 0.014) and subjects without either risk allele (61.8 ± 17.1 years; P = 6.2 × 10(-7)). The association between the presence of the G1 allele and age at initiation of hemodialysis remained statistically significant after adjusting for sociodemographic and other potential confounders. We did not detect an association between the G2 risk allele and age at initiation of hemodialysis, but the sample size was limited. In conclusion, genetic variations in APOL1 identify African Americans that initiate chronic hemodialysis at a younger age. Early interventions to prevent progression of kidney disease may benefit this high-risk population.

Figure 1.

The mean age at dialysis initiation for subjects by APOL1 risk allele status. Because of the proximity of the alleles it is not expected for a diploid sample to have more then two risk alleles, therefore only six groups existed within this dataset: Wt + Wt, Wt + G1, G1 + G1, Wt + G2, G2 + G2, and G1 + G2. Bar height is the mean age. Error bars denote the standard error. *Significantly different from Wt (Wt + Wt).

Figure 2.

Left panel shows the mean age at dialysis initiation by G1 risk allele status in subjects with H-ESRD. Right panel shows age by G1 risk allele status in subjects with other ESRD causes, including HIV, inflammation, toxins, etc. Horizontal bars denote mean age whereas vertical bars denote standard error. *Significantly different from Wt (Wt + Wt).