APOL1 Risk Variants Independently Associated With Early Cardiovascular Disease Death

• Main Authors: Michael D. Hughson, Wendy E. Hoy, Susan A. Mott, John F. Bertram, Cheryl A. Winkler, Jeffrey B. Kopp
• Format: Article
• Language: English
• Published: Elsevier 2018-01-01
• Series: Kidney International Reports
• Subjects: APOL1; cardiovascular disease; hypertension; nephrosclerosis; race
• Online Access: http://www.sciencedirect.com/science/article/pii/S2468024917303613

The relationship of APOL1 renal risk variants to cardiovascular disease (CVD) is controversial and was the subject of this investigation. Methods: Age, cause of death, and nephrosclerosis (the latter defined by glomerulosclerosis) were analyzed in the autopsies of 162 African Americans and 136 whites genotyped for APOL1 risk alleles. Results: Sudden deaths represented >75% of CVD autopsies for both races and all-risk genotypes. The average ages of CVD deaths for African Americans with 1 and 2 APOL1 risk alleles were, respectively, 7.0 years (P = 0.02) and 12.2 years (P < 0.01) younger than African Americans with 0 risk alleles and 8.7 years (P = 0.01) and 13.9 years (P = 0.01) younger than whites. Age differences were not significant between African Americans and whites with 0 risk alleles (P = 0.61). The younger CVD deaths of African Americans were associated with less severe glomerulosclerosis with 2 (P = 0.01), although not 1 (P = 0.09), compared with 0 APOL1 risk alleles. Cardiomyopathy was found in 23% of African Americans with 1 and 2 risk alleles and significantly contributed to the lower age (P = 0.01). For non-CVD deaths, age differences were not seen by race (P = 0.28) or among African Americans by risk allele status (P = 0.38). Conclusion: Carriage of 1 or 2 APOL1 risk alleles in African Americans was associated with earlier age deaths due to coronary artery disease and cardiomyopathy. For 2 risk alleles, the early age was independent of nephrosclerosis.