Population genetics of chronic kidney disease: The evolving story of APOL1

Advances in human genome sequencing and genera- tion of public databases of genomic diversity enable nephrologists to re-examine the genetics of common, complex kidney diseases. Non-diabetic kidney dis- eases prevalent in African ancestry populations and the allelic variation described in chromosome 22q12.3 is one such illustrative example. Newly available ge- nomic database information enabled research groups to discover common functional DNA sequence risk variants in the APOL1 gene. These variants (termed G1 and G2) evolved to confer protection from a spe- cies of trypanosomal infection and thus achieved high prominence in many geographic regions of Africa and have been carried over to African diaspora communi- ties worldwide. Since these discoveries two years ago, new insights have been gained: localization of APOL1 in normal and disease kidney tissues; influence of the APOL1 variants on the histopathology of HIV kidney disease; possible association with kidney transplant durability; onset of kidney failure at a younger age; association with blood lipid concentrations; more pre- cise geographic localization of individuals with these variants to western and southern African ancestry; and the absence of the variants and kidney disease predisposition in Ethiopians. The definition of APOL1 nephropathy also confirms the long-held assumption