APOL1-Associated Kidney Disease in Brazil

Abstract

Introduction Coding variants in apolipoprotein L-1 (APOL1) are associated with an increased risk of end-stage kidney disease (ESRD) in African American individuals under a recessive model of inheritance. The effect of the APOL1 risk alleles on kidney disease has been observed in studies in African American and African populations. Despite the 130 million individuals of recent African ancestry in South America, the impact of APOL1 has not been explored. Methods In this case-control study, we tested APOL1 genotype in 106 Brazilian HD (hemodialysis) patients with African ancestry and compared risk allele frequency with 106 healthy first-degree relatives. The association of risk alleles and ESRD was calculated with a linear mixed model and was adjusted for relatedness and additional confounders. In a broader survey, the age of dialysis initiation and APOL1 variants were analyzed in 274 HD patients. Results Two APOL1 risk alleles were 10 times more common in patients with ESRD than in controls (9.4% vs. 0.9%; odds ratio [OR]: 10.95, SE = 1.49, P = 0.0017). Carriers of 2 risk alleles initiated dialysis 12 years earlier than patients with zero risk alleles. Conclusion The APOL1 risk variants were less frequent in dialysis patients of African ancestry in Brazil than in the United States. Nonetheless, carriers of 2 risk variants had 10-fold higher odds of ESRD. Age of dialysis initiation was markedly lower in 2-risk allele carriers, suggesting a more aggressive disease phenotype. The Brazilian population represents an opportunity to identify different sets of genetic modifiers or environmental triggers that might be present in more extensively studied populations.

The clinical significance of apolipoprotein L1 in head and neck squamous cell carcinoma

“…Apolipoprotein L1 (APOL1) is located at chromosome 22q12.3 and APOL1 gene encodes a trypanolytic factor that dissolves pathogenic Trypanosoma brucei subspecies in humans and gorillas ( 28 ). Other studies have shown a link between non-diabetic nephropathy and variations in the APOL1 gene ( 29 , 30 ), which are also associated with atherosclerosis ( 31 ). APOL1 is one of six genes of the APOL gene family, which are a set of genomic hotspots for various diseases ( 32 ), including schizophrenia, cancer and chronic kidney disease ( 33 , 34 ).…”

Prevalence of APOL1 Risk Variants in Afro-Descendant Patients with Chronic Kidney Disease in a Latin American Country

“…Reports from North America have shown the frequency of APOL1 to be of 20%-39% [13,14]. In contrast, reports from Asiatic and some Latin American countries have shown much lower frequencies (1.9-9.4%) [15,16]. Previous studies have shown that the G1 and G2 APOL1 risk alleles were most common in Western and Southern Africa [2,17].…”

Brazilian Consortium for the Study on Renal Diseases Associated With COVID-19: A Multicentric Effort to Understand SARS-CoV-2-Related Nephropathy

“…Brazil is a country with a large population of Afrodescendants (around 40% of all Brazilians) (18) and the APOL1 high-risk genotype found in Brazil was considered responsible for a more aggressive disease phenotype (23). In addition, the considerable genetic heterogeneity of the Brazilian population and the wide range of possible microenvironments may be highly advantageous for the study of genetic and environmental aspects associated with APOL1.…”