<b><i>APOL1</i></b> Genetic Variants Are Associated with Serum-Oxidized Low-Density Lipoprotein Levels and Subclinical Atherosclerosis in South African CKD Patients

Abstract

Introduction: Apolipoprotein L1 (APOL1) plays an important role in cholesterol metabolism and attenuation of low-density lipoprotein (LDL) oxidation. While protecting against Trypanosoma brucei rhodesiense infection, APOL1 risk alleles confer greater risk for CKD and cardiovascular disease among patients of African descent. Objectives: We investigated whether APOL1 risk variants are associated with atherosclerosis and oxidized LDL (OxLDL) levels among black South African CKD patients. Methods: A cross-sectional study of 120 adult CKD patients and 40 controls was undertaken. DNA samples of participants were genotyped for APOL1 G1 and G2 variants. High-sensitivity C-reactive protein, serum lipids, and OxLDL levels were measured, and carotid doppler ultrasonography was performed on all participants. Results: APOL1 alleles rs73885319, rs60910145, and rs71785313 had minor allele frequencies of 9.2, 8.8, and 17.5%, respectively, in the patients, and 8.8, 8.8, and 13.8%, respectively, in the controls. Of the 9 patients with 2 APOL1 risk alleles, 77.8% were compound G1/G2 heterozygotes and 22.2% were G2 homozygotes. Carriers of at least 1 APOL1 risk allele had a 3-fold increased risk of subclinical atherosclerosis (odds ratio 3.19; 95% confidence interval: 1.64–6.19; p = 0.01) compared to individuals with no risk alleles. Patients with 1 or 2 APOL1 risk alleles showed a significant increase in OxLDL levels when compared with those without the APOL1 risk allele. Conclusion: These findings suggest an increased risk for atherosclerosis in carriers of a single APOL1 risk variant, and the presence of APOL1 risk variants was associated with increased serum OxLDL levels in black South African CKD patients.

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).…”

Cardiovascular disease in chronic kidney disease – a review of risk factors

“…They showed that the APOL1 G1/G2 variants, that decrease autophagosome functions, removal of pro-atherosclerotic cells and clearance of oxidized LDL, significantly increased the burden of atheroscle-rotic CVD in African Americans (JHS and WHI combined, odds ratio, 2.12), suggesting a genetic component to CVD disease in CKD patients of African ancestry [43]. In support of this finding, we recently showed that Black South African CKD patients who are carriers of at least one APOL1 risk allele had a 3-fold increased risk of subclinical atherosclerosis (odds ratio 3.19), and the presence of high-risk APOL1 risk variants was strongly associated with increased oxidized LDL levels [44]. Furthermore, the association between maternal APOL1 genetic variants and pre-eclampsia, an important risk factor for hypertension, CKD and CVD, was explored in pregnant women of African ancestry.…”

New Admixture Patterns Trigger Gene-Environment Mismatch Between APOL1 Risk Alleles And Chronic Kidney Disease Disparities

“…In the Democratic Republic of the Congo, children with APOL1 risk alleles demonstrate early kidney damage [64], and this region of Central West Africa was a major ancestral geographical source for AAs. Additional studies confirming the African origins for these APOL1 variants comes from a second study of children in the Democratic Republic of the Congo [71] where clinical and genetic factors were associated with kidney complications in pediatric patients with sickle cell anemia. Additional studies demonstrating the CKD-associated APOL1 variants as being of African origin come from Cameroon [70] and South Africa [72].…”