APOL1 Nephropathy Risk Variants and Incident Cardiovascular Disease Events in Community-Dwelling Black Adults

Orlando M Gutiérrez; Marguerite R Irvin; Ninad S Chaudhary; Mary Cushman; Neil A Zakai; Victor A David; Sophie Limou; Nathalie Pamir; Alex P Reiner; Rakhi P Naik; Michele M Sale; Monika M Safford; Hyacinth I Hyacinth; Suzanne E Judd; Jeffrey B Kopp; Cheryl A Winkler

doi:10.1161/CIRCGEN.117.002098

APOL1 Nephropathy Risk Variants and Incident Cardiovascular Disease Events in Community-Dwelling Black Adults

Circ Genom Precis Med. 2018 Jun;11(6):e002098. doi: 10.1161/CIRCGEN.117.002098.

Authors

Orlando M Gutiérrez¹, Marguerite R Irvin², Ninad S Chaudhary², Mary Cushman³, Neil A Zakai³, Victor A David⁴, Sophie Limou^{5

6}, Nathalie Pamir⁷, Alex P Reiner⁸, Rakhi P Naik⁹, Michele M Sale¹⁰, Monika M Safford¹¹, Hyacinth I Hyacinth¹², Suzanne E Judd¹³, Jeffrey B Kopp¹⁴, Cheryl A Winkler¹⁵

Affiliations

¹ Department of Medicine, University of Alabama at Birmingham, Birmingham, AL (O.M.G.).
² Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL (M.R.I., N.S.C.).
³ Division of Hematology and Oncology, University of Vermont, Burlington, VT (M.C., N.A.Z.).
⁴ Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD (V.A.D.).
⁵ Basic Research Laboratory, National Cancer Institute, National Institutes of Health, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD (S.L., C.A.W.).
⁶ Center for Research in Immunology and Transplantation, University of Nantes, Nantes, France (S.L.).
⁷ Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR (N.P.).
⁸ Department of Epidemiology, University of Washington, Seattle, WA (A.P.R.).
⁹ Department of Medicine, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD (R.P.N.).
¹⁰ Center for Public Health Genomics, University of Virginia, Charlottesville, VA (M.M. Sale).
¹¹ Division of General Internal Medicine, Weill Cornell Medicine, New York, NY (M.M. Safford).
¹² Department of Pediatrics, Aflac Cancer and Blood Disorder Center, Children's Healthcare of Atlanta, Emory University, Atlanta, GA (H.I.H.).
¹³ Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL (S.E.J.).
¹⁴ Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (J.B.K.). winklerc@mail.nih.gov jeffreyk@intra.niddk.nih.gov.
¹⁵ Basic Research Laboratory, National Cancer Institute, National Institutes of Health, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD (S.L., C.A.W.) winklerc@mail.nih.gov jeffreyk@intra.niddk.nih.gov.

Abstract

Background: APOL1 renal risk variants are strongly associated with chronic kidney disease in Black adults, but reported associations with cardiovascular disease (CVD) have been conflicting.

Methods: We examined associations of APOL1 with incident coronary heart disease (n=323), ischemic stroke (n=331), and the composite CVD outcome (n=500) in 10 605 Black participants of the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Primary analyses compared individuals with APOL1 high-risk genotypes to APOL1 low-risk genotypes in Cox proportional hazards models adjusted for CVD risk factors and African ancestry.

Results: APOL1 high-risk participants were younger and more likely to have albuminuria at baseline than APOL1 low-risk participants. The risk of incident stroke, coronary heart disease, or composite CVD end point did not significantly differ by APOL1 genotype status in multivariable models. The association of APOL1 genotype with incident composite CVD differed by diabetes mellitus status (P_interaction=0.004). In those without diabetes mellitus, APOL1 high-risk genotypes associated with greater risk of incident composite CVD (hazard ratio, 1.67; 95% confidence interval, 1.12-2.47) compared with those with APOL1 low-risk genotypes in multivariable adjusted models. This latter association was driven by ischemic strokes (hazard ratio, 2.32; 95% confidence interval, 1.33-4.07), in particular, those related to small vessel disease (hazard ratio, 5.10; 95% confidence interval, 1.55-16.56). There was no statistically significant association of APOL1 genotypes with incident CVD in subjects with diabetes mellitus. The APOL1 high-risk genotype was associated with higher stroke risk in individuals without but not those with chronic kidney disease in fully adjusted models.

Conclusions: APOL1 high-risk status is associated with CVD events in community-dwelling Black adults without diabetes mellitus.

Keywords: cardiac catheterization; cardiovascular diseases; genetics; myocardial infarction; stroke.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Apolipoprotein L1 / genetics*
Black or African American / genetics*
Cardiovascular Diseases / epidemiology*
Cardiovascular Diseases / etiology
Cardiovascular Diseases / pathology
Female
Genotype
Humans
Incidence
Male
Middle Aged
Mutation*
Renal Insufficiency, Chronic / complications
Renal Insufficiency, Chronic / genetics*
Risk Factors
United States / epidemiology
White People / genetics

Substances

APOL1 protein, human
Apolipoprotein L1

Abstract

Publication types

MeSH terms

Substances

Grants and funding