The Apolipoprotein L1 Gene and Cardiovascular Disease

Area of Science:

• Genetics
• Nephrology
• Cardiology

Background:

• African Americans exhibit a higher incidence of nondiabetic chronic kidney disease (CKD).
• This disparity is largely attributed to two coding renal-risk variants in the apolipoprotein L1 gene (APOL1).
• The APOL1-kidney disease association is independent of hypertension or blood pressure.

Purpose of the Study:

• To review the association between APOL1 renal-risk variants and cardiovascular disease (CVD).
• To explore factors contributing to inconsistent findings regarding APOL1 variants and CVD.
• To consider the impact of APOL1 variants on systemic vasculature and large blood vessels.

Main Methods:

• Literature review of studies investigating APOL1 variants and cardiovascular outcomes.
• Analysis of study-specific factors that may explain disparate results.
• Synthesis of evidence on extra-renal effects of APOL1 G1 and G2 variants.

Main Results:

• APOL1 G1 and G2 variants have been linked to cardiovascular disease, subclinical atherosclerosis, lipoprotein levels, and survival.
• Observed associations between APOL1 variants and CVD risk are inconsistent, ranging from protective to detrimental.
• Disparate findings may stem from study-specific methodologies and populations.

Conclusions:

• APOL1 renal-risk variants may affect the systemic vasculature beyond the kidneys.
• The role of APOL1 variants in cardiovascular disease requires further investigation.
• Understanding APOL1 variant effects on large blood vessels is crucial for developing therapies for APOL1-associated nephropathy and CVD.