Apolipoprotein L1 Risk Genotypes in Ghanaian Systemic Lupus Erythematosus Patients: A Prospective Cohort Study

Abstract

Objective: Two Apolipoprotein L1 (APOL1) risk variants (RV) are enriched in sub-Saharan African populations due to a conferred resistance to Trypanosoma brucei. This comes at the cost of progressive renal disease by multiple causes including systemic lupus erythematosus (SLE). In African Americans, APOL1 high-risk genotypes have emerged as an important risk factor for progressive lupus nephritis. Despite emerging reports that SLE is common in Ghana, where APOL1 variant allelic frequencies are high, the regional contribution to SLE outcomes has not been described. Accordingly, this prospective longitudinal cohort study tested the associations between APOL1 high-risk genotypes and kidney outcomes, organ damage accrual, and death in 100 Ghanaian SLE patients.Methods: A prospective cohort of 100 SLE outpatients met four 1982 American College of Rheumatology SLE criteria. Patients were assessed for demographics, SLE activity, and organ injury as measured by the Systemic Lupus International Collaborating Clinics Damage Index (SDI) at baseline and every 6 months for 1 year. Serum, plasma, and saliva samples were taken for serologic testing and APOL1 genotyping. Outcomes of interest were kidney function, SDI, and case fatality. Results: Assuming a recessive model of inheritance, the APOL1 high-risk genotype (2RV) associated with developing end stage renal disease (ESRD) at an odds ratio of 14 (p=0.008). These patients accrued more SDI points particularly in renal, neurologic, and cardio/pulmonary domains. The SDI was 81.3% higher in 2RV patients compared to 0RV or 1RV patients despite no difference in SLE activity (p=0.02). After a 12 month period of observation, 3/12 (25%) of the 2RV patients died compared to 2/88 (2.3%) of the 0RV or 1RV carriers (odds ratio=13.6, p=0.01). Deaths were due to end stage kidney disease and heart failure. Conclusion: Our results suggest that in Ghanaian SLE patients, APOL1 risk variants are heritable risk factors for morbidity and mortality. Despite no appreciable differences in SLE severity, APOL1 high-risk patients exhibited progressive renal disease, organ damage accrual, and a 13-fold higher case fatality rate.