Abstract 059: Additive effect of the GSTM1(0) Null and APOL1 High Risk Alleles in the African American Study of Kidney Disease (AASK) Trial
Background: Apolipoprotein L-1 (APOL1) G1 and G2 alleles are strongly associated with end stage renal disease (ESRD) in non-diabetic African American (AA) patients. Glutathione-S-transferase Mu 1 (GSTM1) null allele, GSTM1(0), is also associated with accelerated progression of chronic kidney disease (CKD) in hypertensive AA patients. We hypothesized that the GSTM1(0) and APOL1 high risk alleles interact to influence the clinical outcomes in the AASK Trial participants.
Methods: A total of 682 patients were classified into the combination of homozygous null for GSTM1 (0/0), heterozygous (1/0), and homozygous active (1/1) and APOL1 high (High) and low (Low) risk genotypes. The survival differences among the six groups were assessed by log-rank test and in the Cox regression for time to the event of glomerular filtration rate (GFR, 50% or 25ml/min/1.73m2 decline), dialysis, or death, or their composite events. Regression analyses were adjusted for age, gender, proteinuria, baseline GFR, MAP, CVD, drug class, and population admixture.
Results: The 6 groups differed significantly in the time to composite events of GFR, or dialysis or death (log-rank p=0.0033) (Fig. 1). Compared to (1/1)_Low group, the hazard ratios (HR) for the composite events were 2.6 (95% CI 1.27 – 5.32, p=0.009) and 2.4 (95% CI 1.15 – 4.99, p= 0.019) for the (0/0)_Low and the (1/0)_High groups, respectively. The HRs for the other groups did not reach statistical significance [(1/1)_High (HR 1.2, p = 0.73), (1/0)_Low (HR 1.78, p = 0.079), and (0/0)_High (HR 1.91, p = 0.097)].
Conclusion: GSTM1(0) and APOL1 high risk alleles have independent and additive deleterious effects on CKD progression among hypertensive AAs.
Author Disclosures: G. Bodonyi-Kovacs: None. J.Z. Ma: None. M.S. Lipkowitz: None. J.B. Kopp: None. C.A. Winkler: None. T.H. Le: None.
- © 2014 by American Heart Association, Inc.