Association of APOL1 Risk Alleles With Cardiovascular Disease in Blacks in the Million Veteran Program

被引：30

作者：

Bick, Alexander G. ^{[1
,2
,3
]}

Akwo, Elvis ^{[4
,5
]}

Robinson-Cohen, Cassianne ^{[4
,5
]}

Lee, Kyung ^{[6
]}

Lynch, Julie ^{[6
,7
,8
]}

Assimes, Themistocles L. ^{[9
,10
]}

DuVall, Scott ^{[8
]}

Edwards, Todd ^{[4
,5
]}

Fang, Huaying ^{[9
,10
]}

Freiberg, S. Matthew ^{[4
,5
]}

Giri, Ayush ^{[4
,5
]}

Huffman, Jennifer E. ^{[1
]}

Huang, Jie ^{[1
]}

Hull, Leland ^{[1
,6
]}

Kember, Rachel L. ^{[11
,12
]}

Klarin, Derek ^{[1
,2
,3
]}

Lee, Jennifer S. ^{[9
,10
]}

Levin, Michael ^{[11
,12
]}

Miller, Donald R. ^{[6
,13
]}

Natarajan, Pradeep ^{[2
,3
]}

Saleheen, Danish ^{[11
,12
]}

Shao, Qing ^{[6
]}

Sun, Yan V. ^{[14
,15
]}

Tang, Hua ^{[9
,10
]}

Wilson, Otis ^{[4
]}

Chang, Kyong-Mi ^{[11
,12
]}

Cho, Kelly ^{[1
]}

Concato, John ^{[16
]}

Gaziano, J. Michael ^{[1
,17
]}

Kathiresan, Sekar ^{[2
,3
,17
]}

O'Donnell, Christopher J. ^{[1
,17
]}

Rader, Daniel J. ^{[11
]}

Tsao, Philip S. ^{[9
,10
]}

Wilson, Peter W. ^{[14
,15
]}

Hung, Adriana M. ^{[4
,5
]}

Damrauer, Scott M. ^{[11
,12
]}

机构：

[1] Boston VA Healthcare Syst, Boston, MA USA

[2] Massachusetts Gen Hosp, Boston, MA 02114 USA

[3] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[4] Nashville VA Med Ctr, Nashville, TN USA

[5] Vanderbilt Univ, Med Ctr, Nashville, TN USA

[6] Edith Norse Rogers Mem VA Med Ctr, Bedford, MA USA

[7] Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA

[8] VA Informat & Comp Infrastruct, Salt Lake City, UT USA

[9] Palo Alto VA Hlth Care, Palo Alto, CA USA

[10] Stanford Univ, Sch Med, Stanford, CA 94305 USA

[11] Corporal Michael Crescenz VA Med Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA

[12] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA

[13] Boston Univ, Boston, MA 02215 USA

[14] Atlanta VA Med Ctr, Atlanta, GA USA

[15] Emory Univ, Atlanta, GA 30322 USA

[16] VA Connecticut HealthCare Syst, New Haven, CT USA

[17] Harvard Med Sch, Boston, MA 02115 USA

来源：

CIRCULATION | 2019年 / 140卷 / 12期

关键词：

apolipoprotein L1; cardiovascular diseases; genetics; renal insufficiency; chronic; CHOLESTEROL EFFLUX CAPACITY; PHENOME-WIDE ASSOCIATION; CHRONIC KIDNEY-DISEASE; AFRICAN-AMERICAN; VARIANTS; HEART; MORTALITY; RACE;

D O I：

10.1161/CIRCULATIONAHA.118.036589

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Approximately 13% of black individuals carry 2 copies of the apolipoprotein L1 (APOL1) risk alleles G1 or G2, which are associated with 1.5- to 2.5-fold increased risk of chronic kidney disease. There have been conflicting reports as to whether an association exists between APOL1 risk alleles and cardiovascular disease (CVD) that is independent of the effects of APOL1 on kidney disease. We sought to test the association of APOL1 G1/G2 alleles with coronary artery disease, peripheral artery disease, and stroke among black individuals in the Million Veteran Program. Methods: We performed a time-to-event analysis of retrospective electronic health record data using Cox proportional hazard and competing-risks Fine and Gray subdistribution hazard models. The primary exposure was APOL1 risk allele status. The primary outcome was incident coronary artery disease among individuals without chronic kidney disease during the 12.5-year follow-up period. We separately analyzed the cross-sectional association of APOL1 risk allele status with lipid traits and 115 cardiovascular diseases using phenome-wide association. Results: Among 30 903 black Million Veteran Program participants, 3941 (13%) carried the 2 APOL1 risk allele high-risk genotype. Individuals with normal kidney function at baseline with 2 risk alleles had slightly higher risk of developing coronary artery disease compared with those with no risk alleles (hazard ratio, 1.11 [95% CI, 1.01-1.21]; P=0.039). Similarly, modest associations were identified with incident stroke (hazard ratio, 1.20 [95% CI, 1.05-1.36; P=0.007) and peripheral artery disease (hazard ratio, 1.15 [95% CI, 1.01-1.29l; P=0.031). When both cardiovascular and renal outcomes were modeled, APOL1 was strongly associated with incident renal disease, whereas no significant association with the CVD end points could be detected. Cardiovascular phenome-wide association analyses did not identify additional significant associations with CVD subsets. Conclusions: APOL1 risk variants display a modest association with CVD, and this association is likely mediated by the known APOL1 association with chronic kidney disease.

引用

页码：1031 / 1040

页数：10

共 33 条

[1] Race and Socioeconomic Status Independently Affect Risk of Major Amputation in Peripheral Artery Disease [J].

Arya, Shipra ;

Binney, Zachary ;

Khakharia, Anjali ;

Brewster, Luke P. ;

Goodney, Phil ;

Patzer, Rachel ;

Hockenberry, Jason ;

Wilson, Peter W. F. .

JOURNAL OF THE AMERICAN HEART ASSOCIATION, 2018, 7 (02)

[2]

Benjamin EJ, 2019, CIRCULATION, V139, pE56, DOI [10.1161/CIR.0000000000000659, 10.1161/CIR.0000000000000746]

[3] APOL1 G1 genotype modifies the association between HDLC and kidney function in African Americans [J].

Bentley, Amy R. ;

Divers, Jasmin ;

Shriner, Daniel ;

Doumatey, Ayo P. ;

Gutierrez, Orlando M. ;

Adeyemo, Adebowale A. ;

Freedman, Barry I. ;

Rotimi, Charles N. .

BMC GENOMICS, 2015, 16

[4] R PheWAS: data analysis and plotting tools for phenome-wide association studies in the R environment [J].

Carroll, Robert J. ;

Bastarache, Lisa ;

Denny, Joshua C. .

BIOINFORMATICS, 2014, 30 (16) :2375-2376

[5] Association Between APOL1 Genotypes and Risk of Cardiovascular Disease in MESA (Multi-Ethnic Study of Atherosclerosis) [J].

Chen, Teresa K. ;

Katz, Ronit ;

Estrella, Michelle M. ;

Gutierrez, Orlando M. ;

Kramer, Holly ;

Post, Wendy S. ;

Shlipak, Michael G. ;

Wassel, Christina L. ;

Peralta, Carmen A. .

JOURNAL OF THE AMERICAN HEART ASSOCIATION, 2017, 6 (12)

[6]

Chen TK, 2017, ARTERIOSCL THROM VAS, V37, P1765, DOI [10.1161/ATVBAHA.117.309384, 10.1161/atvbaha.117.309384]

[7] Systematic comparison of phenome-wide association study of electronic medical record data and genome-wide association study data [J].

Denny, Joshua C. ;

Bastarache, Lisa ;

Ritchie, Marylyn D. ;

Carroll, Robert J. ;

Zink, Raquel ;

Mosley, Jonathan D. ;

Field, Julie R. ;

Pulley, Jill M. ;

Ramirez, Andrea H. ;

Bowton, Erica ;

Basford, Melissa A. ;

Carrell, David S. ;

Peissig, Peggy L. ;

Kho, Abel N. ;

Pacheco, Jennifer A. ;

Rasmussen, Luke V. ;

Crosslin, David R. ;

Crane, Paul K. ;

Pathak, Jyotishman ;

Bielinski, Suzette J. ;

Pendergrass, Sarah A. ;

Xu, Hua ;

Hindorff, Lucia A. ;

Li, Rongling ;

Manolio, Teri A. ;

Chute, Christopher G. ;

Chisholm, Rex L. ;

Larson, Eric B. ;

Jarvik, Gail P. ;

Brilliant, Murray H. ;

McCarty, Catherine A. ;

Kullo, Iftikhar J. ;

Haines, Jonathan L. ;

Crawford, Dana C. ;

Masys, Daniel R. ;

Roden, Dan M. .

NATURE BIOTECHNOLOGY, 2013, 31 (12) :1102-+

[8] Genetic and Pharmacologic Inactivation of ANGPTL3 and Cardiovascular Disease [J].

Dewey, F. E. ;

Gusarova, V. ;

Dunbar, R. L. ;

O'Dushlaine, C. ;

Schurmann, C. ;

Gottesman, O. ;

McCarthy, S. ;

Van Hout, C. V. ;

Bruse, S. ;

Dansky, H. M. ;

Leader, J. B. ;

Murray, M. F. ;

Ritchie, M. D. ;

Kirchner, H. L. ;

Habegger, L. ;

Lopez, A. ;

Penn, J. ;

Zhao, A. ;

Shao, W. ;

Stahl, N. ;

Murphy, A. J. ;

Hamon, S. ;

Bouzelmat, A. ;

Zhang, R. ;

Shumel, B. ;

Pordy, R. ;

Gipe, D. ;

Herman, G. A. ;

Sheu, W. H. H. ;

Lee, I-T. ;

Liang, K. -W. ;

Guo, X. ;

Rotter, J. I. ;

Chen, Y. -D. I. ;

Kraus, W. E. ;

Shah, S. H. ;

Damrauer, S. ;

Small, A. ;

Rader, D. J. ;

Wulff, A. B. ;

Nordestgaard, B. G. ;

Tybjaerg-Hansen, A. ;

van den Hoek, A. M. ;

Princen, H. M. G. ;

Ledbetter, D. H. ;

Carey, D. J. ;

Overton, J. D. ;

Reid, J. G. ;

Sasiela, W. J. ;

Banerjee, P. .

NEW ENGLAND JOURNAL OF MEDICINE, 2017, 377 (03) :211-221

[9] Association of APOL1 With Heart Failure With Preserved Ejection Fraction in Postmenopausal African American Women [J].

Franceschini, Nora ;

Kopp, Jeffrey B. ;

Barac, Ana ;

Martin, Lisa W. ;

Li, Yun ;

Qian, Huijun ;

Reiner, Alex P. ;

Pollak, Martin ;

Wallace, Robert B. ;

Rosamond, Wayne D. ;

Winkler, Cheryl A. .

JAMA CARDIOLOGY, 2018, 3 (08) :712-720

[10] APOL1 Renal-Risk Variants Do Not Associate With Incident Cardiovascular Disease or Mortality in the Systolic Blood Pressure Intervention Trial [J].

Freedman, Barry I. ;

Rocco, Michael V. ;

Bates, Jeffrey T. ;

Chonchol, Michel ;

Hawfield, Amret T. ;

Lash, James P. ;

Papademetriou, Vasilios ;

Sedor, John R. ;

Servilla, Karen ;

Kimmel, Paul L. ;

Wall, Barry M. ;

Pajewski, Nicholas M. .

KIDNEY INTERNATIONAL REPORTS, 2017, 2 (04) :713-720

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