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Original ArticleChronic Kidney Disease
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Apolipoprotein L1 High-Risk Genotypes and Albuminuria in Sub-Saharan African Populations

Jean-Tristan Brandenburg, Melanie A. Govender, Cheryl A. Winkler, Palwende Romuald Boua, Godfred Agongo, June Fabian and Michèle Ramsay
CJASN June 2022, 17 (6) 798-808; DOI: https://doi.org/10.2215/CJN.14321121
Jean-Tristan Brandenburg
1Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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Melanie A. Govender
1Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
2Division of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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Cheryl A. Winkler
3Molecular Genetic Epidemiology Section, Basic Research Laboratory, Frederick National Laboratory for Cancer Research, Frederick, Maryland
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Palwende Romuald Boua
1Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
4Clinical Research Unit of Nanoro, Institut de Recherche en Sciences de la Santé–DRCO, Nanoro, Burkina Faso
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Godfred Agongo
5Navrongo Health Research Centre, Ghana Health Service, Navrongo, Ghana
6Department of Biochemistry and Forensic Sciences, School of Chemical and Biochemical Sciences, C.K. Tedam University of Technology and Applied Sciences, Navrongo, Ghana
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June Fabian
7Wits Donald Gordon Medical Centre, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
8Medical Research Council/Wits University Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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Michèle Ramsay
1Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
2Division of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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Background and objectives Recessive inheritance of African-specific APOL1 kidney risk variants is associated with higher risk of nondiabetic kidney disease, progression to kidney failure, and early-onset albuminuria that precedes eGFR decline. The effect of APOL1 risk variants on kidney disease in continental Africans is understudied. Objectives of this study were to determine APOL1 risk allele prevalence and associations between APOL1 genotypes and kidney disease in West, East, and South Africa.

Design, setting, participants, & measurements This cross-sectional population-based study in four African countries included 10,769 participants largely aged 40–60 years with sociodemographic and health information, anthropometry data, and blood and urine tests for biomarkers of kidney disease. APOL1 risk alleles were imputed from the H3Africa genotyping array, APOL1 risk allele and genotype frequencies were determined, and genetic associations were assessed for kidney disease. Kidney disease was defined as the presence of eGFR <60 ml/min per 1.73 m2, albuminuria, or a composite end point including eGFR <60 ml/min per 1.73 m2 and/or albuminuria.

Results High G1 allele frequencies occurred in South and West Africa (approximately 7%–13%). G2 allele frequencies were highest in South Africa (15%–24%), followed by West Africa (9%–12%). Associations between APOL1 risk variants and albuminuria were significant for recessive (odds ratio, 1.63; 95% confidence interval, 1.25 to 2.12) and additive (odds ratio, 1.39; 95% confidence interval, 1.09 to 1.76) models. Associations were stronger for APOL1 G1/G1 genotypes versus G0/G0 (odds ratio, 3.87; 95% confidence interval, 2.16 to 6.93) compared with either G2/G2 (odds ratio, 1.65; 95% confidence interval, 1.09 to 2.51) or G1/G2 (odds ratio, 1.24; 95% confidence interval, 0.83 to 1.87). No association between APOL1 risk variants and eGFR <60 ml/min per 1.73 m2 was observed.

Conclusions APOL1 G1 and G2 alleles and high-risk genotype frequencies differed between and within West and South Africa and were almost absent from East Africa. APOL1 risk variants were associated with albuminuria but not eGFR <60 ml/min per 1.73 m2. There may be differential effects of homozygous G1 and G2 genotypes on albuminuria that require further investigation.

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  • albuminuria
  • glomerular filtration rate
  • molecular genetics
  • chronic kidney disease
  • apolipoprotein L1
  • Received November 2, 2021.
  • Accepted March 30, 2022.
  • Copyright © 2022 by the American Society of Nephrology
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Clinical Journal of the American Society of Nephrology: 17 (6)
Clinical Journal of the American Society of Nephrology
Vol. 17, Issue 6
June 2022
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Apolipoprotein L1 High-Risk Genotypes and Albuminuria in Sub-Saharan African Populations
Jean-Tristan Brandenburg, Melanie A. Govender, Cheryl A. Winkler, Palwende Romuald Boua, Godfred Agongo, June Fabian, Michèle Ramsay
CJASN Jun 2022, 17 (6) 798-808; DOI: 10.2215/CJN.14321121

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Apolipoprotein L1 High-Risk Genotypes and Albuminuria in Sub-Saharan African Populations
Jean-Tristan Brandenburg, Melanie A. Govender, Cheryl A. Winkler, Palwende Romuald Boua, Godfred Agongo, June Fabian, Michèle Ramsay
CJASN Jun 2022, 17 (6) 798-808; DOI: 10.2215/CJN.14321121
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