G1 is the major APOL1 risk allele for hypertension-attributed nephropathy in Central Africa

Abstract

Background Sub-Saharan Africans exhibit a higher frequency of chronic kidney disease (CKD) than other populations. In this study, we sought to determine the frequency of apolipoprotein L1 ( APOL1 ) genotypes in hypertension-attributed CKD in Kinshasa, Democratic Republic of the Congo. Methods We performed a case–control study identifying 162 subjects: 79 with hypertension-attributed CKD and 83 controls living in Kinshasa who were genotyped for APOL1 risk variants between July 2013 and November 2016. We selected control subjects from the general population and matched them with the cases according to age. Logistic regression analysis was used to examine the relationship between APOL1 high-risk genotypes and CKD. Results The frequencies of the APOL1 G1 and G2 alleles were 19.1 and 7.1%, respectively. The number of individuals with the G1 and G2 risk alleles was significantly higher in the CKD group (12.7%) than in the control group (2.4%), particularly in individuals with end-stage kidney disease (14.3%). Subjects carrying two risk alleles was strongly and independently associated with hypertension-attributed nephropathy, with an adjusted odds ratio of 7.7 (95% confidence interval 1.5–39.7; P = 0.014). The high-risk APOL1 genotypes were G1/G1 and G1/G2, whereas G2/G2 was not found in the study population. Conclusions The results of this study demonstrate the association of high-risk APOL1 genotypes with kidney disease in Kinshasa. The absence of G2/G2 may be consistent with powerful selective sweeps induced by Trypanosoma brucei gambiense infection. In contrast, the presence of APOL1 G2/G2 among individuals of African ancestry in the USA may indicate relaxation of natural selection in a trypanosome-free environment.

Burden, access and disparities in kidney disease: chronic kidney disease hotspots and progress one step at a time

“…Sumaili et al . [5] largely confirm the association between trypanolytic APOL1 variants and CKD in Kinshasa (Democratic Republic of Congo): subjects carrying two risk alleles had an adjusted odds ratio of 7:7 for hypertension-attributed nephropathy, in line with American studies. However, the high-risk APOL1 genotypes were G1/G1 and G1/G2, whereas G2/G2 was not found in the study population, which differed from thehigher frequency of G2/G2 in the USA.…”

“…Sumaili et al . [5] characterized the association of APOL1 alleles with CKD and end-stage renal disease, and specifically with hypertension-attributed nephropathy in Central Africa. Trypanolytic APOL1 variants were first associated with the high incidence of CKD in US patients of African ancestry 9 years ago and were shown to be mostly associated with human immunodeficiency virus nephropathy and hypertension-attributed CKD [6].…”

Prevalence and Associated Factors of Hypertension Among Adults living in the City of Bandundu, Republic Democratic Republic of the Congo. A Population-Based Cross-Sectional Study.

“…Thus, APOL1 genetic testing can identify young individuals of African ancestry with increased BP burden and risk of hypertension related end-organ damage [40]. A recent study by Sumaili et al from the University of Kinshasa Hospital has reported an association between APOL1 gene renal-risk variants and blood pressure among patients with hypertension-related kidney disease [41,42] and diabete mellitus/obesity are well-known traditional risk factors sharing insulin resistance, sympathetic nervous (SNS) and renin angiotensin aldosterone (RAAS) systems, oxidative stress and subsequent in ammation and endothelial dysfunction as a common pathogenic pathway for cardiac and vascular damage [43].…”

First Case of COVID-19-Associated Collapsing Glomerulopathy in Sub-Saharan Africa

“…Regardless of the associated disease, nearly 70% of these African-descent patients with CG are homozygous for APOL1 risk alleles [ 23 ]. In the Democratic Republic of the Congo, G1 APOL1 risk variants are frequent and are associated with hypertension-attributed nephropathy [ 24 ]. High-risk APOL1 genotype may mediate podocyte damage via up regulation of APOL1 through activation of a viral program in the podocyte, leading to dysregulated endosomal trafficking and autophagic flux, resulting in podocyte depletion and glomerular scarring [ 11 ].…”