APOL1 Nephropathy Risk Alleles and Mortality in African American Adults: A Cohort Study

Abstract

APOL1 nephropathy risk alleles are associated with the development of chronic kidney disease (CKD) in African Americans. Although CKD is an established risk factor for mortality, associations of APOL1 risk alleles with mortality are uncertain. Study Design: Prospective cohort. Settings & Participants: 10,380 African American and 17,485 white American participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. Exposures: APOL1 nephropathy risk alleles. Outcomes: All-cause and cause-specific mortality. Analytical Approach: Cox proportional hazards models were used to examine the association of APOL1 high-risk genotypes (2 risk alleles) versus APOL1 low-risk genotypes (0/1 risk allele) with all-cause and cause-specific mortality in African Americans and examine the risk for all-cause mortality in African Americans with high-risk genotypes versus African Americans with lowrisk genotypes and white Americans. Results: APOL1 high-risk participants were younger and had a higher prevalence of albuminuria than low-risk participants. There was no statistically significant association of APOL1 high-versus low-risk genotypes with all-cause mortality in models adjusted for sociodemographic variables, comorbid conditions, and kidney function (HR, 0.88; 95% CI, 0.77-1.01). After further adjustment for genetic ancestry in a subset with available data, a statistically significant association emerged (HR, 0.81; 95% CI, 0.69-0.96). Associations differed by CKD status (P interaction = 0.04), with African Americans with high-risk genotypes having lower risk for mortality than those with low-risk genotypes in fully adjusted models (HR, 0.78; 95% CI, 0.62-0.99) among those with CKD, but not those without CKD (HR, 0.84; 95% CI, 0.66-1.05). Compared with white Americans, African Americans with high-risk genotypes had a similar rate of mortality, whereas African Americans with low-risk genotypes had a higher rate of mortality (HR, 1.07; 95% CI, 1.00-1.14) in fully adjusted models. Limitations: Lack of follow-up measures of kidney function. Conclusions: African Americans with high-risk APOL1 genotypes had lower mortality than those with low-risk genotypes in multivariableadjusted models including genetic ancestry. Complete author and article information provided before references.

A 7-gene signature predicts the prognosis of patients with bladder cancer

“…APOL1 is mainly active in the kidney [ 33 ], and its high expression can promote the occurrence of kidney disease [ 34 ]. In the study of Gutiérrez OM et al, the mortality rate of patients with a high-risk APOL1 genotype was significantly lower than that of patients with low-risk genotypes in the prognostic review cohort of chronic kidney disease [ 35 ]. However, there are few reports about the effect of APOL1 on BC, and further research is still needed.…”

Toward a fine-scale population health monitoring system

“…Knowledge about genetic variation shared across human populations can aid in understanding the demographic events that might impact disease burden across populations. For ll example, variants in the APOL1 gene, which confer a substantially increased risk of kidney disease and cardiovascular disease, arose in Africa; were first discovered in African American (AA) populations (Kao et al, 2008;Parsa et al, 2013); and are mainly studied in African (Hassan et al, 2020;Ekrikpo et al, 2020;Thakoordeen-Reddy et al, 2020;Nqebelele et al, 2019) or AA (Miller et al, 2020;Umeukeje and Young, 2019;Gutié rrez et al, 2020) populations. However, APOL1 risk variants exist at appreciable frequencies among many populations across the Americas that historically share African genetic ancestry, but may not self-identify as African or AA, and are subsequently underrepresented in APOL1 research (Nadkarni et al, 2018;Kramer et al, 2017).…”

A 7-gene signature predicts the prognosis of patients with bladder cancer

“…APOL1 is mainly active in the kidney 33 , and its high expression can promote the occurrence of kidney disease 34 . In the study of Gutiérrez OM et al, the mortality rate of patients with a high-risk APOL1 genotype was signi cantly lower than that of patients with low-risk genotypes in the prognostic review cohort of chronic kidney disease 35 . However, there are few reports about the effect of APOL1 on BC, and further research is still needed.…”