Session Type: ACR Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: African Americans (AA) with systemic lupus erythematous (SLE) are at higher risk for both renal disease and avascular necrosis (AVN). The two Apolipoprotein L1 (APOL1) risk variants (RV), G1 and G2, have been associated with chronic kidney disease and atherosclerosis in AAs and are responsible for excess renal risk in this population. We therefore investigated the association between carriers of the risk variants and prevalence of AVN in AA SLE patients.
Methods: Our retrospective cohort study of 113 AA SLE patients addressed the hypothesis that APOL1 variants increase the risk of avascular necrosis. Subjects were recruited from three high volume urban SLE clinical sites. This IRB-approved study included patients over 18 years of age, of self-reported AA ancestry, meeting at least four of the American College of Rheumatology (ACR) revised criteria for SLE. PCR/sequencing was used to stratify subjects by APOL1 genotype. Medical charts including clinical notes and imaging reports were reviewed for documentation of avascular necrosis. Subjects were stratified into groups with zero, one or two risk alleles. Association between presence of AVN and APOL1 risk allele, basic demographic characteristics and duration of SLE disease were evaluated using logistic regression analysis via R statistical software.
Results: The frequencies of the G0, G1, and G2 alleles were 0.6, 0.22, and 0.18 respectively. Of the 113 patients 18 (16%) had documented AVN. Higher proportion of patients with documented AVN n = 16 (89%) had at least one risk APOL1 allele present vs those without AVN n = 59 (62%). There were no significant differences for age and gender between patients with and without AVN. Presence of one APOL1 allele trended towards increased risk of AVN (p=0.081), having two APOL1 risk alleles (p=0.016) and longer disease duration (p< 0.001) were associated with increased risk of AVN. Having one APOL1 risk allele (p=0.011) or two risk APOL1 risk alleles (p=0.003) and disease duration (p< 0.001) were significant when adjusted for age in multivariable logistic model. APOL1 variant alleles were associated with AVN in a dose dependent relationship with homozygotes variant carriers having the highest prevalence (OR 31.4 95% CI 3.25-303.63, p=0.003). BMI, average disease activity, corticosteroid use, presence of nephritis and ESRD were not associated with presence of AVN.
Conclusion: Our analysis suggests higher risk of avascular necrosis among African American SLE patients who are carriers of APOL1 risk allele. Given the high allelic frequencies of these variants in African Americans, this relationship may underpin the observed association of AVN with Black race. Further work is necessary to uncover the mechanism of this association.
To cite this abstract in AMA style:Yip K, Efuni E, Qian Y, Clancy R, Buyon J, Blazer A. Avascular Necrosis Is Associated with APOL1 Variants in African Americans with Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/avascular-necrosis-is-associated-with-apol1-variants-in-african-americans-with-systemic-lupus-erythematosus/. Accessed November 28, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/avascular-necrosis-is-associated-with-apol1-variants-in-african-americans-with-systemic-lupus-erythematosus/