Cardiovascular Twist to the Rapidly Evolving Apolipoprotein L1 Story

Abstract

Blacks form the largest (13%) ethnic minority group in the United States with predominant ancestry from subsaharan Africa. This group experiences multiple health disparities, for example, they have relatively high death rates for chronic kidney disease, cardiovascular disease (CVD), and stroke with hypertension as a particularly prevalent risk factor. An appreciable proportion of the disparity can be explained by inequalities in social and environmental factors, but there remains plenty of room for population-level differences in genetic susceptibility to make an important contribution. To test this hypothesis, Ito and colleagues1 have undertaken DNA sequence analysis of a candidate apolipoprotein gene ( APOL1 ) in black cohorts and report ancestry-specific genetic associations with CVD. The decision to examine APOL1 in this context is in itself an intriguing tale that merits reflection. Article, see p 845 The apolipoprotein L gene family comprises 6 genes clustered on human chromosome 22q.2 Apolipoprotein L1 is the only member that includes a signal peptide, and with apolipoprotein A1, is secreted into a particularly dense subspecies (HDL3) of high-density lipoprotein (HDL) particles.3 APOL1 , along with its immediate genomic neighbors APOL2, APOL3 , and APOL4 , has only been found in primate genomes.4 All 6 apolipoprotein L genes contain characteristic protein domains that imply important intracellular physiological roles possibly involving ion transport and apoptosis.5 Primates benefit from the innate immune ability of apolipoprotein L1 to lyse the Trypanosoma brucei brucei protozoa that cause African trypanosomiasis (sleeping sickness).6 This lysis property is derived from the affinity of apolipoprotein for lysosomal membranes where it …