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Arterioscler Thromb Vasc Biol. 2016 Feb;36(2):398-403. doi: 10.1161/ATVBAHA.115.305970. Epub 2015 Dec 3.

APOL1 Genotype, Kidney and Cardiovascular Disease, and Death in Older Adults.

Author information

1
From the Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (K.J.M., J.T., D.J.F., M.R.P.); Veterans Affairs San Diego Healthcare System and Division of Nephrology-Hypertension, University of California San Diego School of Medicine (J.H.I.); Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (L.H.K.); and Department of Pathology and Laboratory Medicine, University of Vermont, Burlington (R.P.T.). kmukamal@bidmc.harvard.edu.
2
From the Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (K.J.M., J.T., D.J.F., M.R.P.); Veterans Affairs San Diego Healthcare System and Division of Nephrology-Hypertension, University of California San Diego School of Medicine (J.H.I.); Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (L.H.K.); and Department of Pathology and Laboratory Medicine, University of Vermont, Burlington (R.P.T.).

Abstract

OBJECTIVE:

We sought to evaluate the cardiovascular impact of coding variants in the apolipoprotein L1 gene APOL1 that protect against trypanosome infection but have been associated with kidney disease among African Americans.

APPROACH AND RESULTS:

As part of the Cardiovascular Health Study, a population-based cohort of Americans aged ≥65 years, we genotyped APOL1 polymorphisms rs73885319 and rs71785153 and examined kidney function, subclinical atherosclerosis, and incident cardiovascular disease and death over 13 years of follow-up among 91 African Americans with 2 risk alleles, 707 other African Americans, and 4964 white participants. The high-risk genotype with 2 risk alleles was associated with 2-fold higher levels of albuminuria and lower ankle-brachial indices but similar carotid intima-media thickness among African Americans. Median survival among high-risk African Americans was 9.9 years (95% confidence interval [CI], 8.7-11.9), compared with 13.6 years (95% CI, 12.5-14.3) among other African Americans and 13.3 years (95% CI, 13.0-13.6) among whites (P=0.03). The high-risk genotype was also associated with increased risk for incident myocardial infarction (adjusted hazard ratio 1.8; 95% CI, 1.1-3.0) and mortality (adjusted hazard ratio 1.3; 95% CI 1.0-1.7). Albuminuria and risk for myocardial infarction and mortality were nearly identical between African Americans with 0 to 1 risk alleles and whites.

CONCLUSIONS:

APOL1 genotype is associated with albuminuria, subclinical atherosclerosis, incident myocardial infarction, and mortality in older African Americans. African Americans without 2 risk alleles do not differ significantly in risk of myocardial infarction or mortality from whites. APOL1 trypanolytic variants may account for a substantial proportion of the excess risk of chronic disease in African Americans.

KEYWORDS:

albuminuria; apolipoproteins; epidemiology; genetics; kidney; myocardial infarction

PMID:
26634651
PMCID:
PMC4732891
DOI:
10.1161/ATVBAHA.115.305970
[Indexed for MEDLINE]
Free PMC Article

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