Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: Two Apolipoprotein L1 (APOL1) risk variants (RV), G1 and G2, located on chromosome 22q12.3, have been associated with excess renal risk in African Americans (AA). The strongest correlations are in those with comorbid infectious or inflammatory diseases such as HIV or SLE collapsing glomerulonephropathy potentially owing to increased gene expression in the setting of chronic inflammation. APOL1 related cardiovascular disease (CVD) risk has been more controversial. Of four large, population-based studies, two reported 2-8 fold increased CVD in RV homozygotes while two others reported no increased risk. APOL1 associated CVD has never been assessed in a cohort with comorbid inflammatory disease. Accordingly, this retrospective cohort study evaluates prevalent CVD across APOL1 genotypes in SLE patients to test the hypothesis that the APOL1 cardiovascular phenotype is more penetrant in an SLE population.
Methods: PCR/sequencing was completed in 92 AA SLE patients. Subjects were stratified by genotype: ancestral (G0/G0), RV heterozygotes (RV/G0), and RV homozygotes (RV/RV). Clinical CVD endpoints including both cardiac: congestive heart failure, arrhythmia, and left ventricular hypertrophy; and atherosclerotic: coronary artery disease, myocardial infarction, peripheral vascular disease, vascular calcifications, and carotid artery disease were assessed by chart review. Logistic regression was used to test associations between the genotypes and a composite CVD end point defined by meeting one or more of the above parameters. Secondary analysis of atherosclerotic vs cardiac end points was also completed.
Conclusion: The undulating inflammation of SLE plays an important role in each step of atherogeneisis from endothelial dysfunction to plaque rupture. In RV carriers, it may also increase the toxic protein burden leading to an amplified propensity towards CVD. Taken together, the RV is associated with prevalent CVD in this AA SLE cohort suggesting that SLE may be an important “second hit” in the relationship between APOL1 RV and CVD.
To cite this abstract in AMA style:Blazer A, Clancy RM, Belmont HM, Izmirly PM, Markham A, Buyon JP. Apolipoprotein L1 Risk Variants Associate with Prevalent Cardiovascular Disease in African American Systemic Lupus Erythematous Patients [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/apolipoprotein-l1-risk-variants-associate-with-prevalent-cardiovascular-disease-in-african-american-systemic-lupus-erythematous-patients/. Accessed March 3, 2021.
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