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Abstract: TH-PO812

APOL1 Genetic Variants Are Associated with Increased Risk of Coronary Artery Disease and Sudden Cardiac Death: An Autopsy Study in Sudden Death Registry

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Guo, Liang, CVPath Institute, Gaithersburg, Maryland, United States
  • Delsante, Marco, University of Parma, Parma, Italy
  • Cornelissen, Anne, CVPath Institute, Gaithersburg, Maryland, United States
  • Zhao, Xiaoqing, CVPath Institute, Gaithersburg, Maryland, United States
  • Kolodgie, Frank David, CVPath Institute, Gaithersburg, Maryland, United States
  • Shin, Myung, Merck & Co., Inc, Kenilworth, New Jersey, United States
  • Hoek, Maarten, Merck & Co., Inc, Kenilworth, New Jersey, United States
  • Kopp, Jeffrey B., National Institute of Diabetes and Digestive and Kidney Disease, National Institute of Health, Bethesda, Maryland, United States
  • Rosenberg, Avi Z., Johns Hopkins University, Baltimore, Maryland, United States
  • Davis, Harry R., CVPath Institute, Gaithersburg, Maryland, United States
  • Virmani, Renu, CVPath Institute, Gaithersburg, Maryland, United States
  • Finn, Aloke, CVPath Institute, Gaithersburg, Maryland, United States
Background

Two genetic risk variants (G1 and G2) in APOL1, which encodes apolipoprotein L1, have been associated with kidney disease in African Americans, but whether these variants are associated with coronary artery disease or sudden cardiac death is conflicting.

Methods

Here we determined the APOL1 genotype (G0, G1, or G2) for 687 African Americans from the Sudden Death Registry of CVPath Institute. The cause of death was determined through cardiac autopsy and histopathology analyses, and categorized as sudden coronary death with or without coronary thrombosis (n=269), cardiac (non-coronary) death (n=174), and other causes (n=244). Genotyping revealed risk variants of APOL1 in 396 patients with 306 patients carrying 1 risk allele (182 G0/G1, 124 G0/G2), and 90 patients harboring 2 risk alleles (28 G1/G1, 46 G1/G2, 16 G2/G2). The APOL1 reference allele (G0/G0) was observed in 291 patients.

Results

Carriers of APOL1 risk alleles had a significantly increased risk of coronary thrombosis (relative risk 1.2006, ; 95% confidence interval, 1.0003 to 1.4409), particularly of coronary plaque rupture (relative risk, 1.2425; 95% confidence interval, 1.0136 to 1.5230). Individuals with only one risk allele (G0/G1 or G0/G2) still had significantly increased risk of coronary plaque rupture (relative risk, 1.2980; 95% confidence interval, 1.0083 to 1.6708). Further analyses suggested risk allele and hypertension are two independent factors contributing to plaque rupture. Moreover, carriers of G2 risk allele had a higher risk of cardiac causes of death (relative risk, 1.5040; 95% confidence interval, 1.0430 to 2.1705). Histopathologic analysis of the kidneys in selected age and gender matched 50 G0/G0 carriers and 50 carriers of two risk alleles showed borderline significant increases of glomerular density (p=0.08) and microcystic tubular dilation (p=0.07). A significantly higher global glomerulosclerosis was seen in carriers of two risk alleles (p=0.049), and the glomerulosclerosis is correlated with the coronary artery plaque burden (p=0.035).

Conclusion

The APOL1 high risk status is associated with higher risk of plaque rupture in coronary artery disease and sudden cardiac death.

Funding

  • Veterans Affairs Support