The Apolipoprotein L1 Gene and Cardiovascular Disease

Relative to those with European ancestry, African Americans have an excess incidence of nondiabetic chronic kidney disease predominantly due to two coding renal-risk variants in the apolipoprotein L1 gene (APOL1). This APOL1–kidney disease association is independent of systemic hypertension or blood pressure. Recent reports describe extra-renal effects of the APOL1 G1 and G2 renal-risk variants on cardiovascular disease (CVD), subclinical atherosclerosis, lipoprotein particle concentrations, and survival. However, results have been less consistent than those seen in kidney disease, and the observed APOL1 associations with CVD vary from risk to protective. This manuscript reviews the relationships between APOL1 renal-risk variants and CVD, with an emphasis on study-specific factors that may have contributed to disparate observations. It is possible that APOL1 renal-risk variants impact the systemic vasculature, not only the kidneys. As novel therapies for APOL1-associated nephropathy are developed, APOL1 variant protein effects on large blood vessels and risk of CVD will need to be considered.