Apolipoprotein L1 risk genotypes in Ghanaian patients with systemic lupus erythematosus: a prospective cohort study
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Date
2021
Journal Title
Journal ISSN
Volume Title
Publisher
BMJ
Abstract
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 (SELENASLEDAI) 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.
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.
Description
Research Article