Apolipoprotein L1 risk genotypes in Ghanaian patients with systemic lupus erythematosus: a prospective cohort study

Abstract

Objective: Two apolipoprotein L1 (APOL1) risk variants (RV) are enriched in sub-Saharan African populations due to conferred resistance to Trypanosoma brucei. These variants associate with adverse renal outcomes by multiple causes including SLE. 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 patients with SLE.

Methods: This was a prospective cohort study of 100 SLE outpatients who sought care at Korle bu Teaching Hospital in Accra, Ghana. Adult patients who met 4 American College of Rheumatology criteria for SLE were genotyped for APOL1 and followed longitudinally for SLE activity as measured by the Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) hybrid and organ injury as measured by the Systemic Lupus International Collaborating Clinics Damage Index (SDI) at baseline and every 6 months for 1 year. Outcomes of interest were kidney function, SDI and case fatality.

Results: Assuming a recessive inheritance, the APOL1 high-risk genotype (2RV) associated with end-stage renal disease (ESRD) at an OR of 14 (p=0.008). These patients accrued more SDI points particularly in renal and neurological domains. The SDI was 81.3% higher in 2RV patients compared with 0RV or 1RV patients despite no difference in SLE activity (p=0.01). After a 12-month period of observation, 3/12 (25%) of the 2RV patients died compared with 2/88 (2.3%) of the 0RV or 1RV carriers (OR=13.6, p=0.01). Deaths were due to end-stage kidney disease and heart failure.

Conclusion: APOL1 RVs were heritable risk factors for morbidity and mortality in this Ghanaian SLE cohort. Despite no appreciable differences in SLE activity, APOL1 high-risk patients exhibited progressive renal disease, organ damage accrual and a 13-fold higher case fatality.

Keywords: cardiovascular diseases; genetic; lupus erythematosus; lupus nephritis; polymorphism; systemic.

Figure 1

SLICC Damage Index (SDI) across APOL1 genotype: stacked bar chart visualising the mean SDI points accrued by genotype group (0RV in blue, 1RV in orange, 2RV in grey). Each damage criterion is ordered by affected organ system (shown to the left). APOL1, apolipoprotein L1; RV, risk variant.

Figure 2

Distribution of kidney function parameters by APOL1 genotype and time point. (A) The bars represent the proportion of patients in each urine dipstick range (0+−3–4+). The x-axis represents percentages, and the y-axis represents the genotype groups by time point (0M=month zero, 6M=month 6, 12M=month 12). At each time point, the proportion of patients in the higher dipstick propteinuria ranges was higher in the 2RV patients. These differences did not reach statistical significance. (B) The box plots represent the distribution of mean arterial pressure (mm Hg) values by genotype groups and time point. Overall, 2RV patients exhibited significantly higher mean arterial pressure values (p=0.01). (C) The box plots represent the distribution of mean eGFR (mL/min) values by genotype groups and time point. Overall, 2RV patients exhibited significantly lower eGFR values (p=0.01). **P=0.01. APOL1, apolipoprotein L1; eGFR, estimated glomerular filtration rate; RV, risk variant.

Figure 3

Case fatality rate by APOL1 genotype. (A) Bars represent each genotype group (0RV, 1RV or 2RV). The y-axis represents the percentage of patients in that genotype group who died, and the x-axis shows the study time point. **P<0.01. (B) Table represents the causes of death at each time point by genotype group. APOL1, apolipoprotein L1; ESRD, end-stage renal disease; Pulm, pulmonary; RV, risk variant.