APOL1 Genetic Variants Are Associated With Increased Risk of Coronary Atherosclerotic Plaque Rupture in the Black Population
Author
Cornelissen, AnneFuller, Daniela T
Fernandez, Raquel
Zhao, Xiaoqing
Kutys, Robert
Binns-Roemer, Elizabeth
Delsante, Marco
Sakamoto, Atsushi
Paek, Ka Hyun
Sato, Yu
Kawakami, Rika
Mori, Masayuki
Kawai, Kenji
Yoshida, Teruhiko
Latt, Khun Zaw
Miller, Clint L
de Vries, Paul S
Kolodgie, Frank D
Virmani, Renu
Shin, Myung Kyun
Hoek, Maarten
Heymann, Jurgen
Kopp, Jeffrey B
Rosenberg, Avi Z
Davis, Harry R
Guo, Liang
Finn, Aloke V
Date
2021-05-27Journal
Arteriosclerosis, Thrombosis, and Vascular BiologyPublisher
Lippincott Williams and WilkinsType
Article
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Show full item recordAbstract
Objective: Reported associations between kidney risk variants (G1 and G2) in APOL1 (apolipoprotein L1), encoding APOL1, and cardiovascular disease have been conflicting. We sought to explore associations of APOL1 risk variants with cause of sudden death using the CVPath Sudden Death Autopsy Registry. Approach and Results: APOL1 haplotypes and causes of sudden death, as determined through autopsy and histopathology, were obtained for 764 Black subjects. Genotyping revealed APOL1 risk alleles in 452 of 764 (59%) subjects with 347 (77%) subjects carrying one risk allele and 105 (23%) subjects harboring 2 risk alleles. APOL1 risk allele carrier status was associated with a significantly increased risk of coronary thrombosis due to plaque rupture, versus noncarriers (odds ratio for rupture, 1.655 [95% CI, 1.079-2.539]; P=0.021). Histological examinations showed coronary plaques in carriers of 2 APOL1 risk alleles had larger necrotic cores compared with noncarriers (necrotic core area/total plaque area: 46.79%±6.47% versus 20.57%±5.11%; P=0.0343 in ruptured plaques, and 41.48%±7.49% versus 18.93%±3.97%; P=0.0342 in nonruptured plaques), and immunohistochemical and immunofluorescent staining revealed APOL1-positive areas localized primarily to the necrotic core. Conclusions: APOL1 risk alleles were independently associated with an increased risk of thrombotic coronary death due to plaque rupture. Our results suggest that carriers of both 1 and 2 APOL1 risk alleles have greater accumulation of APOL1 protein within culprit plaques and greater necrotic core sizes than noncarriers. These findings suggest that APOL1 plays a role in determining plaque stability. © 2021 Lippincott Williams and Wilkins. All rights reserved.Identifier to cite or link to this item
http://hdl.handle.net/10713/16126ae974a485f413a2113503eed53cd6c53
10.1161/ATVBAHA.120.315788
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