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

Rasheed A Gbadegesin; Ifeoma Ulasi; Samuel Ajayi; Yemi Raji; Timothy Olanrewaju; Charlotte Osafo; Adebowale D Ademola; Adanze Asinobi; Cheryl A Winkler; David Burke; Fatiu Arogundade; Ivy Ekem; Jacob Plange-Rhule; Manmak Mamven; Michael Matekole; Olukemi Amodu; Richard Cooper; Sampson Antwi; Adebowale A Adeyemo; Titilayo O Ilori; Victoria Adabayeri; Alexander Nyarko; Anita Ghansah; Toyin Amira; Adaobi Solarin; Olugbenga Awobusuyi; Paul L Kimmel; Frank Chip Brosius; Muhammad Makusidi; Uzoma Odenigbo; Matthias Kretzler; Jeffrey B Hodgin; Martin R Pollak; Vincent Boima; Barry I Freedman; Nicholette D Palmer; Bernard Collins; Milind Phadnis; Jill Smith; Celia I Agwai; Ogochukwu Okoye; Aliyu Abdu; Jillian Wilson; Winfred Williams; Babatunde L Salako; Rulan S Parekh; Bamidele Tayo; Dwomoa Adu; Akinlolu Ojo; H3Africa Kidney Disease Research Network

doi:10.1056/NEJMoa2404211

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

N Engl J Med. 2024 Oct 26. doi: 10.1056/NEJMoa2404211. Online ahead of print.

Authors

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

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
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.).

Abstract

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