APOL1 Genetic Variants Are Associated with Increased Risk of Coronary Atherosclerotic Plaque Rupture in the Black Population

Anne Cornelissen, Daniela T. Fuller, Raquel Fernandez, Xiaoqing Zhao, Robert Kutys, Elizabeth Binns-Roemer, Marco Delsante, Atsushi Sakamoto, Ka Hyun Paek, Yu Sato, Rika Kawakami, Masayuki Mori, Kenji Kawai, Teruhiko Yoshida, Khun Zaw Latt, Clint L. Miller, Paul S. De Vries, Frank D. Kolodgie, Renu Virmani, Myung Kyun ShinMaarten Hoek, Jurgen Heymann, Jeffrey B. Kopp, Avi Z. Rosenberg, Harry R. Davis, Liang Guo, Aloke V. Finn

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2201-2214
Number of pages14
JournalArteriosclerosis, thrombosis, and vascular biology
DOIs
StateAccepted/In press - 2021

Keywords

  • apolipoprotein
  • cardiovascular disease
  • coronary artery disease
  • kidney
  • plaque, atherosclerotic

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint

Dive into the research topics of 'APOL1 Genetic Variants Are Associated with Increased Risk of Coronary Atherosclerotic Plaque Rupture in the Black Population'. Together they form a unique fingerprint.

Cite this