. 2025 Jan 16;392(3):228-238.

doi: 10.1056/NEJMoa2404211. Epub 2024 Oct 26.

APOL1 Bi- and Monoallelic Variants and Chronic Kidney Disease in West Africans

Rasheed A Gbadegesin¹, Ifeoma Ulasi¹, Samuel Ajayi¹, Yemi Raji¹, Timothy Olanrewaju¹, Charlotte Osafo¹, Adebowale D Ademola¹, Adanze Asinobi¹, Cheryl A Winkler¹, David Burke¹, Fatiu Arogundade¹, Ivy Ekem¹, Jacob Plange-Rhule¹, Manmak Mamven¹, Michael Matekole¹, Olukemi Amodu¹, Richard Cooper¹, Sampson Antwi¹, Adebowale A Adeyemo¹, Titilayo O Ilori¹, Victoria Adabayeri¹, Alexander Nyarko¹, Anita Ghansah¹, Toyin Amira¹, Adaobi Solarin¹, Olugbenga Awobusuyi¹, Paul L Kimmel¹, Frank Chip Brosius¹, Muhammad Makusidi¹, Uzoma Odenigbo¹, Matthias Kretzler¹, Jeffrey B Hodgin¹, Martin R Pollak¹, Vincent Boima¹, Barry I Freedman¹, Nicholette D Palmer¹, Bernard Collins¹, Milind Phadnis¹, Jill Smith¹, Celia I Agwai¹, Ogochukwu Okoye¹, Aliyu Abdu¹, Jillian Wilson¹, Winfred Williams¹, Babatunde L Salako¹, Rulan S Parekh¹, Bamidele Tayo¹, Dwomoa Adu¹, Akinlolu Ojo¹; H3Africa Kidney Disease Research Network

Collaborators, Affiliations

Collaborators

H3Africa Kidney Disease Research Network:
Gloria Ashuntantang, Francois Kaze Folefack, Hermine Fouda, Georgette Guemkam Georgette Guemkam, Rulan S Parekh, Dwomoa Adu, Vincent Boima, Charlotte Osafo, Victoria Adabayeri, Edward Kwakyi, P Mensah Amoah, Michael Matekole, Alexander Nyarko, Anita Ghansah, Sampson Antwi, Elliot Koranteng Tannor, Perditer Okyere, Jacob Plange-Rhule, Manmak Mamven, Samuel Ajayi, Babatunde L Salako, Adebowale D Ademola, Olukemi Amodu, Yemi Raji, Adanze Asinobi, Toyin Amira, Babawale Bello, Rotimi W Braimoh, Chris Esezobor, Adaobi Solarin, Olugbenga Awobusuyi, Theophilus Umezudike, Debo Adekoya, Mumuni Amisu, Ayoola Odeyemi, Oshomah-Bello Oluwatosin, Fatiu Arogundade, Oluyomi Okunola, Abubakr Sanusi, Wasiu Olowu, Bolanle Omotoso, Hassan Muzamil, Timothy Olanrewaju, C O Bewaji, A Chijioke, Olanrewaji Adedoyin, Ifeoma Ulasi, Ugochi Onu, Edwin Okafor, Chinwuba Ijoma, Aliyu Abdu, Sanusi M Bala, Patience Obiagwu, Ademola Babatunde, Abdullahi Mudi, Aisha Nalado, Adamu Usman, Charles Odenigbo, Ifeoma Modebe, Nonyelun Jisieike-Onuigbo, Hyacinth Eze, Chinelo Nduka, Franklin Ifiora, John Aneke, Agu Nkiru, Odenigbo Uzoma, Ogochukwu Okoye, Patrick Ekpebe, Muhammad Makusidi, Aminu Sakajiki Muhammad, Hamidu Muhammad Liman, Saddiku Sahabi, Fatima Nma Jiya Bello, Goronyo Yahaya, Lawal Olumoyiwa, Mignon McCulloch, David Burke, Matthias Kretzler, Jeffrey B Hodgin, Adebowale Adeyemo, Paul L Kimmel, Martin R Pollak, Titilayo O Ilori, Bernard Collins, Winfred Williams, Bamidele Tayo, Richard Cooper, Rasheed A Gbadegesin, Cheryl A Winkler, Milind Phadnis, Jill Smith, Celia I Agwai, Akinlolu Ojo, Olugbenga Ogedegbe, Jillian Wilson, Frank Chip Brosius, Barry I Freedman, Nicole D Palmer

Affiliation

¹ From the Department of Pediatrics, Duke University Medical Center, Durham (R.A.G.), and the Departments of Medicine (B.I.F.) and Biochemistry (N.D.P.), Wake Forest University School of Medicine, Winston-Salem - both in North Carolina; the Department of Medicine, University of Nigeria, Nsukka (I.U.), the Department of Medicine, College of Medicine, University of Ibadan, Ibadan (S. Ajayi, Y.R., A.D.A., A. Asinobi, O. Amodu, B.L.S.), the Department of Medicine, University of Ilorin, Ilorin (T.O.), the Department of Medicine, Obafemi Awolowo University, Ile-Ife (F.A.), the Department of Medicine, University of Abuja, Abuja, Nigeria (M. Mamven), the Department of Medicine, College of Medicine, University of Lagos, Lagos (T.A.), the Department of Medicine, College of Medicine, Lagos State University, Ojo (A.S., O. Awobusuyi), the Department of Medicine, Usmanu Danfodiyo University, Sokoto (M. Makusidi), Nnamdi Azikiwe University Teaching Hospital, Nnewi (U.O.), Delta State University Teaching Hospital, Oghara (O.O.), and Aminu Kano Teaching Hospital, Kano (A. Abdu) - all in Nigeria; the Department of Medicine, University of Ghana Medical School (C.O., M. Matekole, V.A., V.B., D.A.), and Noguchi Memorial Institute for Medical Research, University of Ghana (A.N., A.G.), Accra, the Department of Medicine, University of Cape Coast, Cape Coast (I.E.), and Kwame Nkrumah University of Science and Technology, Kumasi (J.P.-R., S. Antwi) - all in Ghana; the Basic Research Laboratory, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (C.A.W.), the Center for Research on Genomics and Global Health, National Human Genome Research Institute (A.A.A.), and the Division of Kidney, Urologic and Digestive Disease, National Institute of Diabetes and Digestive Kidney Diseases (P.L.K.), National Institutes of Health, Bethesda - all in Maryland; the Departments of Human Genetics (D.B.), Medicine (M.K.), and Pathology (J.B.H.), University of Michigan Medical School, Ann Arbor; the Parkinson School of Health Sciences and Public Health, Loyola University, Chicago (R.C., B.T.); the Department of Medicine, Boston University School of Medicine (T.O.I.), the Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School (M.R.P.), and the Departments of Pathology (B.C.) and Medicine (W.W.), Massachusetts General Hospital and Harvard Medical School - all in Boston; the Department of Medicine, College of Medicine, University of Arizona, Tucson (F.C.B.); the Departments of Biostatistics and Data Science (M.P., J.S.) and Medicine (C.I.A., J.W., A.O.), University of Kansas Medical Center, Kansas City, Kansas; and the Department of Medicine and Pediatrics, Women's College Hospital, Hospital for Sick Children and University of Toronto, Toronto (R.S.P.).

PMID: 39465900
PMCID: PMC11735277
DOI: 10.1056/NEJMoa2404211

APOL1 Bi- and Monoallelic Variants and Chronic Kidney Disease in West Africans

Rasheed A Gbadegesin et al. N Engl J Med. 2025.

. 2025 Jan 16;392(3):228-238.

doi: 10.1056/NEJMoa2404211. Epub 2024 Oct 26.

Authors

Collaborators

H3Africa Kidney Disease Research Network:
Gloria Ashuntantang, Francois Kaze Folefack, Hermine Fouda, Georgette Guemkam Georgette Guemkam, Rulan S Parekh, Dwomoa Adu, Vincent Boima, Charlotte Osafo, Victoria Adabayeri, Edward Kwakyi, P Mensah Amoah, Michael Matekole, Alexander Nyarko, Anita Ghansah, Sampson Antwi, Elliot Koranteng Tannor, Perditer Okyere, Jacob Plange-Rhule, Manmak Mamven, Samuel Ajayi, Babatunde L Salako, Adebowale D Ademola, Olukemi Amodu, Yemi Raji, Adanze Asinobi, Toyin Amira, Babawale Bello, Rotimi W Braimoh, Chris Esezobor, Adaobi Solarin, Olugbenga Awobusuyi, Theophilus Umezudike, Debo Adekoya, Mumuni Amisu, Ayoola Odeyemi, Oshomah-Bello Oluwatosin, Fatiu Arogundade, Oluyomi Okunola, Abubakr Sanusi, Wasiu Olowu, Bolanle Omotoso, Hassan Muzamil, Timothy Olanrewaju, C O Bewaji, A Chijioke, Olanrewaji Adedoyin, Ifeoma Ulasi, Ugochi Onu, Edwin Okafor, Chinwuba Ijoma, Aliyu Abdu, Sanusi M Bala, Patience Obiagwu, Ademola Babatunde, Abdullahi Mudi, Aisha Nalado, Adamu Usman, Charles Odenigbo, Ifeoma Modebe, Nonyelun Jisieike-Onuigbo, Hyacinth Eze, Chinelo Nduka, Franklin Ifiora, John Aneke, Agu Nkiru, Odenigbo Uzoma, Ogochukwu Okoye, Patrick Ekpebe, Muhammad Makusidi, Aminu Sakajiki Muhammad, Hamidu Muhammad Liman, Saddiku Sahabi, Fatima Nma Jiya Bello, Goronyo Yahaya, Lawal Olumoyiwa, Mignon McCulloch, David Burke, Matthias Kretzler, Jeffrey B Hodgin, Adebowale Adeyemo, Paul L Kimmel, Martin R Pollak, Titilayo O Ilori, Bernard Collins, Winfred Williams, Bamidele Tayo, Richard Cooper, Rasheed A Gbadegesin, Cheryl A Winkler, Milind Phadnis, Jill Smith, Celia I Agwai, Akinlolu Ojo, Olugbenga Ogedegbe, Jillian Wilson, Frank Chip Brosius, Barry I Freedman, Nicole D Palmer

Affiliation

¹ From the Department of Pediatrics, Duke University Medical Center, Durham (R.A.G.), and the Departments of Medicine (B.I.F.) and Biochemistry (N.D.P.), Wake Forest University School of Medicine, Winston-Salem - both in North Carolina; the Department of Medicine, University of Nigeria, Nsukka (I.U.), the Department of Medicine, College of Medicine, University of Ibadan, Ibadan (S. Ajayi, Y.R., A.D.A., A. Asinobi, O. Amodu, B.L.S.), the Department of Medicine, University of Ilorin, Ilorin (T.O.), the Department of Medicine, Obafemi Awolowo University, Ile-Ife (F.A.), the Department of Medicine, University of Abuja, Abuja, Nigeria (M. Mamven), the Department of Medicine, College of Medicine, University of Lagos, Lagos (T.A.), the Department of Medicine, College of Medicine, Lagos State University, Ojo (A.S., O. Awobusuyi), the Department of Medicine, Usmanu Danfodiyo University, Sokoto (M. Makusidi), Nnamdi Azikiwe University Teaching Hospital, Nnewi (U.O.), Delta State University Teaching Hospital, Oghara (O.O.), and Aminu Kano Teaching Hospital, Kano (A. Abdu) - all in Nigeria; the Department of Medicine, University of Ghana Medical School (C.O., M. Matekole, V.A., V.B., D.A.), and Noguchi Memorial Institute for Medical Research, University of Ghana (A.N., A.G.), Accra, the Department of Medicine, University of Cape Coast, Cape Coast (I.E.), and Kwame Nkrumah University of Science and Technology, Kumasi (J.P.-R., S. Antwi) - all in Ghana; the Basic Research Laboratory, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (C.A.W.), the Center for Research on Genomics and Global Health, National Human Genome Research Institute (A.A.A.), and the Division of Kidney, Urologic and Digestive Disease, National Institute of Diabetes and Digestive Kidney Diseases (P.L.K.), National Institutes of Health, Bethesda - all in Maryland; the Departments of Human Genetics (D.B.), Medicine (M.K.), and Pathology (J.B.H.), University of Michigan Medical School, Ann Arbor; the Parkinson School of Health Sciences and Public Health, Loyola University, Chicago (R.C., B.T.); the Department of Medicine, Boston University School of Medicine (T.O.I.), the Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School (M.R.P.), and the Departments of Pathology (B.C.) and Medicine (W.W.), Massachusetts General Hospital and Harvard Medical School - all in Boston; the Department of Medicine, College of Medicine, University of Arizona, Tucson (F.C.B.); the Departments of Biostatistics and Data Science (M.P., J.S.) and Medicine (C.I.A., J.W., A.O.), University of Kansas Medical Center, Kansas City, Kansas; and the Department of Medicine and Pediatrics, Women's College Hospital, Hospital for Sick Children and University of Toronto, Toronto (R.S.P.).

PMID: 39465900
PMCID: PMC11735277
DOI: 10.1056/NEJMoa2404211

Abstract

Background: Apolipoprotein L1 gene (APOL1) variants are risk factors for chronic kidney disease (CKD) among Black Americans. Data are sparse on the genetic epidemiology of CKD and the clinical association of APOL1 variants with CKD in West Africans, a major group in the Black population.

Methods: We conducted a case-control study involving participants from Ghana and Nigeria who had CKD stages 2 through 5, biopsy-proven glomerular disease, or no kidney disease. We analyzed the association of CKD with APOL1 variants among participants with high-risk genotypes (two APOL1 risk alleles) and those with low-risk genotypes (fewer than two APOL1 risk alleles) by fitting logistic-regression models that controlled for covariates, including clinical site, age, and sex.

Results: Among 8355 participants (4712 with CKD stages 2 through 5, 866 with glomerular diseases, and 2777 with no kidney disease), the prevalence of monoallelic APOL1 variants was 43.0% and that of biallelic APOL1 variants was 29.7%. Participants with two APOL1 risk alleles had higher odds of having CKD than those with one risk allele or no risk alleles (adjusted odds ratio, 1.25; 95% confidence interval [CI], 1.11 to 1.40), as well as higher odds of focal segmental glomerulosclerosis (adjusted odds ratio, 1.84; 95% CI, 1.30 to 2.61). Participants with one APOL1 risk allele had higher odds of having CKD than those with no risk alleles (adjusted odds ratio, 1.18; 95% CI, 1.04 to 1.33), as well as higher odds of focal segmental glomerulosclerosis (adjusted odds ratio, 1.61; 95% CI, 1.04 to 2.48). The inclusion of covariates did not modify the association of monoallelic and biallelic APOL1 variants with CKD or focal segmental glomerulosclerosis.

Conclusions: In this study, monoallelic APOL1 variants were associated with 18% higher odds of CKD and 61% higher odds of focal segmental glomerulosclerosis; biallelic APOL1 variants were associated with 25% higher odds of CKD and 84% higher odds of focal segmental glomerulosclerosis. (Funded by the National Human Genome Research Institute and others.).

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Figures

**Figure 1Panel A:. Association of High-risk *APOL1* Genotype with CKD Among 8,355 West Africans in the Human Heredity and Health in Africa (H3Africa) Kidney Disease Research Network**
Note: Forest plot for the association between biallelic *APOL1* high-risk genotype and CKD showed significant odds of CKD among individuals with 2 *APOL1* risk variants compared with those with 1 or 0 risk variant. The adjusted odds of disease increase with worsening CKD stages and the odds was higher in participants with biopsy-proven FSGS. #: G0/G1, G0/G2, G0/G0

**Figure 1 Panel B:. Association of One *APOL1* Risk Variant with CKD Among 8,355 West Africans in the Human Heredity and Health in Africa (H3Africa) Kidney Disease Research Network**
Note: Forest plot showing higher odds of developing CKD in participants with single disease risk variant (G1/G0, G2/G0) versus those with no risk variant (G0/G0). Similar pattern was observed for participants with biopsy-proven FSGS.

See this image and copyright information in PMC

Comment in

APOL1 Bi- and Monoallelic Variants and Chronic Kidney Disease in West Africans.
Zhou XJ. Zhou XJ. N Engl J Med. 2025 Apr 24;392(16):1663. doi: 10.1056/NEJMc2502038. N Engl J Med. 2025. PMID: 40267443 No abstract available.
APOL1 Bi- and Monoallelic Variants and Chronic Kidney Disease in West Africans.
Ingwiller M. Ingwiller M. N Engl J Med. 2025 Apr 24;392(16):1663-1664. doi: 10.1056/NEJMc2502038. N Engl J Med. 2025. PMID: 40267444 No abstract available.
APOL1 Bi- and Monoallelic Variants and Chronic Kidney Disease in West Africans. Reply.
Gbadegesin RA, Adu D, Ojo A. Gbadegesin RA, et al. N Engl J Med. 2025 Apr 24;392(16):1664. doi: 10.1056/NEJMc2502038. N Engl J Med. 2025. PMID: 40267445 No abstract available.

References

1. GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2020;395:709–733. - PMC - PubMed
1. Stanifer JW, Jing B, Tolan S, et al. The epidemiology of chronic kidney disease in sub-Saharan Africa: a systematic review and meta-analysis. The Lancet Global Health 2014;2:e174–e81. - PubMed
1. Coresh J, Selvin E, Stevens LA, et al. Prevalence of chronic kidney disease in the United States. Jama 2007;298:2038–47. - PubMed
1. Saran R, Robinson B, Abbott KC, et al. US Renal Data System 2019 Annual Data Report: Epidemiology of Kidney Disease in the United States. American journal of kidney diseases : the official journal of the National Kidney Foundation 2020;75:A6–A7. - PubMed
1. Tzur S, Rosset S, Shemer R, et al. Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene. Human genetics 2010;128:345–50. - PMC - PubMed

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APOL1 Bi- and Monoallelic Variants and Chronic Kidney Disease in West Africans

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APOL1 Bi- and Monoallelic Variants and Chronic Kidney Disease in West Africans

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