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Circ Res. 2014 Feb 28;114(5):845-50. doi: 10.1161/CIRCRESAHA.114.302347. Epub 2013 Dec 30.

Increased burden of cardiovascular disease in carriers of APOL1 genetic variants.

Author information

1
From the Department of Genetics, Harvard Medical School, Boston, MA (K.I., A.G.B., M.G.P., S.R.D., J.N.H., J.G.S., C.S.); Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge (K.I., A.G.B., J.F., G.G., N.G., S.B.G., C.N.-C., S.K., J.N.H., D.M.A., M.R.P., J.G.S., C.S.); Center for Human Genetic Research, Massachusetts General Hospital, Boston (J.F., C.N.-C., S.K., D.M.A.); Division of Nephrology, Department of Medicine (D.J.F., G.G., M.R.P.) and Center for Vascular Biology Research, Department of Medicine (D.J.F.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Departments of Medicine (H.A.T., E.R.F.) and Physiology and Biophysics (J.G.W.), University of Mississippi Medical Center, Jackson; Jackson State University, MS (H.A.T.); Tougaloo College, MS (H.A.T.); Cardiology Division, Massachusetts General Hospital, Boston (C.N.-C., S.K.); Divisions of Genetics and Endocrinology and Program in Genomics, Children's Hospital, Boston, MA (J.N.H.); and Howard Hughes Medical Institute and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (C.S.).

Abstract

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(-6)). 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(-4)). 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(-3); JHS and WHI combined, P=8.5×10(-5); 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.

KEYWORDS:

atherosclerosis; continental population groups; epidemiology; genetics; renal insufficiency, chronic; risk factors

PMID:
24379297
PMCID:
PMC3982584
DOI:
10.1161/CIRCRESAHA.114.302347
[Indexed for MEDLINE]
Free PMC Article

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