Increased Burden of Cardiovascular Disease in Carriers of APOL1 Genetic Variants

• Published in: Circulation research Vol. 114; no. 5; pp. 845 - 850
• Main Authors: Ito, Kaoru, Bick, Alexander G, Flannick, Jason, Friedman, David J, Genovese, Giulio, Parfenov, Michael G, DePalma, Steven R, Gupta, Namrata, Gabriel, Stacey B, Taylor, Herman A, Fox, Ervin R, Newton-Cheh, Christopher, Kathiresan, Sekar, Hirschhorn, Joel N, Altshuler, David M, Pollak, Martin R, Wilson, James G, Seidman, J.G, Seidman, Christine
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 28.02.2014
• Subjects: Adult; Aged; Apolipoprotein L1; Apolipoproteins - genetics; Atherosclerosis - ethnology; Atherosclerosis - genetics; Black or African American - genetics; Black or African American - statistics & numerical data; Female; Genetic Predisposition to Disease - ethnology; Genetic Predisposition to Disease - genetics; Genetic Variation; Humans; Incidence; Lipoproteins, HDL - genetics; Male; Middle Aged; Renal Insufficiency, Chronic - ethnology; Renal Insufficiency, Chronic - genetics; Risk Factors; atherosclerosis; epidemiology; risk factors; genetics; renal insufficiency, chronic; continental population groups
• ISSN: 0009-7330; 1524-4571; 1524-4571
• DOI: 10.1161/CIRCRESAHA.114.302347

RATIONALE:Two distinct alleles in the gene encoding apolipoprotein L1 (APOL1), a major component of high-density lipoprotein, confer protection against Trypanosoma brucei rhodesiense infection and also increase risk for chronic kidney disease. Approximately 14% of Americans with African ancestry carry 2 APOL1 risk alleles, accounting for the high chronic kidney disease burden in this population. OBJECTIVE:We tested whether APOL1 risk alleles significantly increase risk for atherosclerotic cardiovascular disease (CVD) in African Americans. METHODS AND RESULTS:We sequenced APOL1 in 1959 randomly selected African American participants in the Jackson Heart Study (JHS) and evaluated associations between APOL1 genotypes and renal and cardiovascular phenotypes. Previously identified association between APOL1 genotypes and chronic kidney disease was confirmed (P=2.4×10). Among JHS participants with 2 APOL1 risk alleles, we observed increased risk for CVD (50/763 events among participants without versus 37/280 events among participants with 2 risk alleles; odds ratio, 2.17; P=9.4×10). We replicated this novel association of APOL1 genotype with CVD in Women’s Health Initiative (WHI) participants (66/292 events among participants without versus 37/101 events among participants with 2 risk alleles; odds ratio, 1.98; P=8.37×10; JHS and WHI combined, P=8.5×10; odds ratio, 2.12). The increased risk for CVD conferred by APOL1 alleles was robust to correction for both traditional CVD risk factors and chronic kidney disease. CONCLUSIONS:APOL1 variants contribute to atherosclerotic CVD risk, indicating a genetic component to cardiovascular health disparities in individuals of African ancestry. The considerable population of African Americans with 2 APOL1 risk alleles may benefit from intensive interventions to reduce CVD.