Abstract TP466: Apolipoprotein L1 Gene Risk Variants Are Not Associated With Increased Volume of Brain Lesions

Abstract

Background: There are conflicting data regarding the association between apolipoprotein L1 gene (APOL1) risk variants and cardiovascular disease. Some data suggest a protective effect of APOL1 variants on subclinical atherosclerosis, despite an increase in the risk of kidney disease in African American patients. We sought to further explore this potentially paradoxical association. Methods: This is a secondary analysis of Systolic Blood Pressure Intervention Trial (SPRINT). We included African American patients who had APOL1 renal-risk variants genotyped. The primary outcome is volumetric measurements of lesions in four brain components: white matter (WM), gray matter (GM), basal ganglia (BG), and total brain (TB). The primary predictor is APOL1 risk genotype. We fit linear regression models to the primary outcomes and adjusted for age, sex, cigarette smoking, diabetes, hypertension, African ancestry admixture, and total brain volume. Results: We included 215 patients, with a mean (SD) age of 65.0 (7.8) years. The number of patients with 0, 1, and 2 APOL1 variants was 86, 105, and 24. The mean values for the volumetric measurements are seen in Table 1, which were not statistically different. The adjusted regression models did not show a significant relationship between APOL1 status and white matter lesions (β coef -0.36, 95% CI -1.20-0.48, p=0.398), gray matter lesions (β coef -0.002, 95% CI -0.07-0.07, p=0.945), basal ganglia lesions (β coef -0.01, 95% CI -0.03-0.02, p=0.542), or total brain lesions (β coef -0.36, 95% CI -1.21-0.49, p=0.403). Conclusion: There is no association between APOL1 risk variants and brain lesions in African American patients. These data support prior studies that found no relationship between APOL1 and chronic microvascular disease or brain volume. Despite these findings, further research would be needed to fully disprove an association, given conflicting reports in the literature and the smaller sample size of this study.