APOL1 genotyping is incomplete without testing for the protective M1 modifier p.N264K variant
Rasheed Gbadegesin, Elena Martinelli, Yask Gupta, David J. Friedman, Matthew G. Sampson, Martin R. Pollak, Simone Sanna‐Cherchi
Abstract
Focal segmental glomerulosclerosis (FSGS), a pattern of injury seen in some patients with nephrotic syndrome, is a leading cause of chronic kidney disease (CKD) especially in people of African ancestry [1].In 2008, using the method of Mapping by Admixture Linkage Disequilibrium (MALD), two studies discovered a locus on chromosome 22 as the genetic driver of high prevalence of hypertension associated end stage kidney disease (H-ESKD) and FSGS in African Americans [2,3].Fine mapping of the region later showed that two variants in apolipoprotein L1(APOL1), G1 (rs73885319: p.S342G and rs60910145: p.I384M) and G2 (rs71785313: a 6 base-pair deletion), when inherited in homozygous or compound heterozygous pattern, are driving this major risk [4,5].APOL1 is