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

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, w...

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Autores principales:	Ashira Blazer, Ida Dzifa Dey, Janet Nwaukoni, Margaret Reynolds, Festus Ankrah, Huda Algasas, Tasneem Ahmed, Jasmin Divers
Formato:	article
Lenguaje:	EN
Publicado:	BMJ Publishing Group 2021
Materias:	Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/4a9cb6266e80412ba9affb80b039a5b7
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spelling	oai:doaj.org-article:4a9cb6266e80412ba9affb80b039a5b72021-11-17T04:00:06ZApolipoprotein L1 risk genotypes in Ghanaian patients with systemic lupus erythematosus: a prospective cohort study10.1136/lupus-2020-0004602053-8790https://doaj.org/article/4a9cb6266e80412ba9affb80b039a5b72021-11-01T00:00:00Zhttps://lupus.bmj.com/content/8/1/e000460.fullhttps://doaj.org/toc/2053-8790Objective 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.Ashira BlazerIda Dzifa DeyJanet NwaukoniMargaret ReynoldsFestus AnkrahHuda AlgasasTasneem AhmedJasmin DiversBMJ Publishing GrouparticleImmunologic diseases. AllergyRC581-607ENLupus Science and Medicine, Vol 8, Iss 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607
spellingShingle	Immunologic diseases. Allergy RC581-607 Ashira Blazer Ida Dzifa Dey Janet Nwaukoni Margaret Reynolds Festus Ankrah Huda Algasas Tasneem Ahmed Jasmin Divers Apolipoprotein L1 risk genotypes in Ghanaian patients with systemic lupus erythematosus: a prospective cohort study
description	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.
format	article
author	Ashira Blazer Ida Dzifa Dey Janet Nwaukoni Margaret Reynolds Festus Ankrah Huda Algasas Tasneem Ahmed Jasmin Divers
author_facet	Ashira Blazer Ida Dzifa Dey Janet Nwaukoni Margaret Reynolds Festus Ankrah Huda Algasas Tasneem Ahmed Jasmin Divers
author_sort	Ashira Blazer
title	Apolipoprotein L1 risk genotypes in Ghanaian patients with systemic lupus erythematosus: a prospective cohort study
title_short	Apolipoprotein L1 risk genotypes in Ghanaian patients with systemic lupus erythematosus: a prospective cohort study
title_full	Apolipoprotein L1 risk genotypes in Ghanaian patients with systemic lupus erythematosus: a prospective cohort study
title_fullStr	Apolipoprotein L1 risk genotypes in Ghanaian patients with systemic lupus erythematosus: a prospective cohort study
title_full_unstemmed	Apolipoprotein L1 risk genotypes in Ghanaian patients with systemic lupus erythematosus: a prospective cohort study
title_sort	apolipoprotein l1 risk genotypes in ghanaian patients with systemic lupus erythematosus: a prospective cohort study
publisher	BMJ Publishing Group
publishDate	2021
url	https://doaj.org/article/4a9cb6266e80412ba9affb80b039a5b7
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Apolipoprotein L1 risk genotypes in Ghanaian patients with systemic lupus erythematosus: a prospective cohort study

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