APOL1 Sends Its REGARDS to Cardiovascular Disease
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See Article by Gutiérrez and Irvin et al
In recent years, our understanding of chronic kidney disease (CKD) risk in patients of African ancestry has dramatically increased with the identification of common high-risk variants in the APOL1 gene.1,2 Although CKD is known to be a risk factor for atherosclerotic cardiovascular disease (ASCVD),3 whether APOL1 nephropathy risk variants also influence cardiovascular outcomes remains unclear as previous data are conflicting. In this analysis of the REGARDS (REasons for Geographic And Racial Differences in Stroke) study, Gutiérrez et al4 report that APOL1 high-risk genotypes are not associated with ASCVD risk in the overall cohort but may have significant associations with ASCVD in nondiabetic individuals, as well as in those without CKD.
APOL1 is a gene located on the long arm of chromosome 22 encoding primate-specific APOL1 (apolipoprotein L1), which lyses the parasite Trypanosoma brucei that causes African sleeping sickness.1 Two evolutionarily recent APOL1 variants (G1 and G2) have allowed humans to keep up in the arms race against T. brucei and its subspecies that had developed resistance against APOL1.1,2 The G1 and G2 alleles, which were introduced into the human genome after European ancestors are thought to have left Africa, have conferred a survival advantage in individuals homozygous or heterozygous for either the G1 or G2 allele and thus have become prevalent among native Africans and blacks.3 This phenomenon has come at a cost: human genetic studies have shown that individuals who are homozygous or compound heterozygotes for the risk alleles (high-risk genotype) are at significantly higher risk of developing CKD, particularly focal segmental glomerulosclerosis and HIV-associated nephropathy.5,6 Recent work suggests that APOL1 …