APOL1 Genetic Variants Are Associated With Increased Risk of Coronary Atherosclerotic Plaque Rupture in the Black Population.
APOL1 Genetic Variants Are Associated With Increased Risk of Coronary Atherosclerotic Plaque Rupture in the Black Population.
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DOI：
10.1161/atvbaha.120.315788
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发表时间：
2021-07
期刊：
影响因子：
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通讯作者：
Finn AV
中科院分区：
文献类型：
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作者：
Cornelissen A;Fuller DT;Fernandez R;Zhao X;Kutys R;Binns-Roemer E;Delsante M;Sakamoto A;Paek KH;Sato Y;Kawakami R;Mori M;Kawai K;Yoshida T;Latt KZ;Miller CL;de Vries PS;Kolodgie FD;Virmani R;Shin MK;Hoek M;Heymann J;Kopp JB;Rosenberg AZ;Davis HR;Guo L;Finn AV
Reported associations between kidney risk variants (G1 and G2) in APOL1, encoding apolipoprotein L1 (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. APOL1 haplotypes and causes of sudden death, as determined through autopsy and histopathology, were obtained for 764 African Americans. Genotyping revealed APOL1 risk alleles in 452 of 764 (59%) subjects with 347 (77%) subjects carrying one risk allele and 105 (23%) subjects harboring two risk alleles. APOL1 risk allele carrier status was associated with a significantly increased risk of coronary thrombosis due to plaque rupture, versus non-carriers (OR for rupture 1.655, 95% CI 1.079 – 2.539; p = 0.021). Histological examinations showed coronary plaques in carriers of two APOL1 risk alleles had larger necrotic cores compared to non-carriers (necrotic core area/total plaque area: 46.79% ± 6.47% vs. 20.57% ± 5.11%; p = 0.0343 in ruptured plaques, and 41.48% ± 7.49% vs. 18.93% ± 3.97%; p = 0.0342 in non-ruptured plaques), and immunohistochemical and immunofluorescent staining revealed APOL1-positive areas localized primarily to the necrotic core. 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 one and two APOL1 risk alleles have greater accumulation of APOL1 protein within culprit plaques and greater necrotic core sizes than non-carriers. These findings suggest that APOL1 plays a role in determining plaque stability.
