Background and objectives apo L1 (APOL1) nephropathy risk alleles are associated with CKD in blacks. Although APOL1 has innate immune functions, little is known about the association of APOL1 genotypes with risk of infectious outcomes, such as sepsis. The objective of this study was to examine the associations of APOL1 nephropathy risk alleles with risk of sepsis in black adults. Design, setting, participants, & measurements We assessed the association of APOL1 risk alleles with incident sepsis in 10,366 black participants of the Reasons for Geographic and Racial Differences in Stroke study enrolled between 2003 and 2007 with follow-up through December 31, 2012. In Cox models adjusted for demographics, comorbid conditions, and principal components ancestry, we examined the association of APOL1 risk alleles with incident sepsis using recessive (comparing zero or one versus two risk alleles), dominant (zero versus one or two risk alleles), and additive genetic models. We also examined models stratified by diabetes and CKD status. Results A total of 1320 (13%) participants had two APOL1 risk alleles, 4719 (46%) had one risk allele, and 4327 (42%) participants had zero risk alleles. A total of 306 sepsis events occurred over a median 6.5 years (interquartile range, 4.5–8.1). There were no statistically significant associations of APOL1 genotype with sepsis risk under recessive genetic models. APOL1 genotypes were associated with sepsis risk under dominant (hazard ratio, 1.55; 95% confidence interval, 1.13 to 2.11) and additive (hazard ratio per variant allele copy, 1.25; 95% confidence interval, 1.02 to 1.53) genetic models adjusted for covariates and ancestry. These associations did not vary by diabetes or CKD status (Pinteraction.0.10 for both). Conclusions In community-dwelling black adults, carriage of APOL1 nephropathy risk alleles are common and associated with higher risk of sepsis.
|Number of pages||8|
|Journal||Clinical Journal of the American Society of Nephrology|
|State||Published - Dec 6 2019|
Bibliographical noteFunding Information:
Departments of 1Epidemiology, 4Biostatistics, and 11Medicine, University of Alabama at Birmingham, Birmingham, Alabama; 2Division of Public Health Sciences, Department of Surgery, Washington University, St. Louis, Missouri; 3Departments of Medicine and Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, Vermont; 5Department of Medicine, Johns Hopkins University, Baltimore, Maryland; 6Nantes University, French National Institute of Health and Medical Research, Center for Research in Transplantation and Immunology, Nantes, France; 7Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado; 8Department of Emergency Medicine, University of Texas Health Science Center at Houston, Houston, Texas; 9Basic Research Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland; and 10Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
Dr. Gutiérrez was supported by grants from the National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) (K24DK116180) and NINDS (R01NS080850). Dr. Kopp was supported by the Intramural Research Program, NIDDK, NIH. Dr. Wang was supported by a grant from the National Institute of Nursing Research (R01 NR012726). Dr. Winkler was funded in part with federal funds from the National Cancer Institute (NCI), NIH, under contract HHSN26120080001E, and supported in part by the Intramural Research Program of the NIH, NCI, Center for Cancer Research. Dr. Zakai was supported by the Reasons for Geographic and Racial Differences in Stroke grant from the National Heart, Lung, and Blood Institute (K08 HL096841). This research project is supported by a cooperative agreement cofunded by NINDS and NIA, NIH, US DHHS (U01 NS041588). This work was also supported by grants from the Center for Clinical and Translational Science and the Lister Hill Center for Health Policy of the University of Alabama at Birmingham.
Dr. Gutiérrez reports receiving grant support and consulting fees from Keryx Biopharmaceuticals, grant support and consulting fees from Amgen, and grant support from GSK, outside of the submitted work. Dr. Kopp reports receiving nonfinancial research project support from Merck. Dr. Naik reports receiving funding from Elsevier. Dr. Chaudhary, Dr. Irvin, Dr. Lange, Dr. Moore, and Dr. Winkler have nothing to disclose.
© 2019 by the American Society of Nephrology.
ASJC Scopus subject areas
- Critical Care and Intensive Care Medicine