APOL1s

APOL1s refers to two distinct genes, APOL1 and APOL1. These genes encode apolipoprotein L1, a protein that plays a role in lipid metabolism and immune responses. Variations within the APOL1 gene are strongly associated with an increased risk of developing certain kidney diseases, particularly focal segmental glomerulosclerosis (FSGS) and hypertension-associated nephropathy.

These genetic variations are most prevalent in individuals of recent African ancestry. It is hypothesized that these APOL1 variants may have conferred a survival advantage in certain historical environments, such as those with high exposure to the parasite Trypanosoma brucei rhodesiense, which causes African trypanosomiasis (sleeping sickness). The APOL1 protein is thought to have some protective effect against this parasite.

However, in the absence of such parasitic pressure, these same APOL1 variants become detrimental and significantly elevate the risk for chronic kidney disease. The exact mechanisms by which APOL1 variants contribute to kidney damage are still under investigation but are believed to involve cellular stress, inflammation, and impaired lipid transport within the kidney cells. Research into APOL1 is a significant area in understanding kidney disease pathogenesis and developing targeted therapies.