APOL1 Nephropathy Risk Alleles and Risk of Sepsis in Blacks

• Published in: Clinical journal of the American Society of Nephrology 2019-12, Vol.14 (12), p.1733-1740
• Main Authors: Chaudhary, Ninad S, Moore, Justin X, Zakai, Neil A, Judd, Suzanne E, Naik, Rakhi P, Limou, Sophie, Cushman, Mary, Lange, Leslie A, Wang, Henry E, Winkler, Cheryl A, Irvin, Marguerite R, Kopp, Jeffrey B, Gutiérrez, Orlando M
• Format: Article
• Language: English
• Subjects: Aged; Alleles; Apolipoprotein L1 - genetics; Black or African American; Black People - genetics; Female; Genotype; Humans; Life Sciences; Male; Middle Aged; Original; Renal Insufficiency, Chronic - etiology; Renal Insufficiency, Chronic - genetics; Sepsis - etiology; Sepsis - genetics
• ISSN: 1555-9041; 1555-905X; 1555-905X
• DOI: 10.2215/CJN.04490419

apo L1 ( ) nephropathy risk alleles are associated with CKD in blacks. Although APOL1 has innate immune functions, little is known about the association of genotypes with risk of infectious outcomes, such as sepsis. The objective of this study was to examine the associations of nephropathy risk alleles with risk of sepsis in black adults. We assessed the association of 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 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. A total of 1320 (13%) participants had two 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 genotype with sepsis risk under recessive genetic models. 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 ( >0.10 for both). In community-dwelling black adults, carriage of nephropathy risk alleles are common and associated with higher risk of sepsis.