TY - JOUR
T1 - APOL1 Bi- and Monoallelic Variants and Chronic Kidney Disease in West Africans
AU - H3Africa Kidney Disease Research Network
AU - Gbadegesin, Rasheed A.
AU - Ulasi, Ifeoma
AU - Ajayi, Samuel
AU - Raji, Yemi
AU - Olanrewaju, Timothy
AU - Osafo, Charlotte
AU - Ademola, Adebowale D.
AU - Asinobi, Adanze
AU - Winkler, Cheryl A.
AU - Burke, David
AU - Arogundade, Fatiu
AU - Ekem, Ivy
AU - Plange-Rhule, Jacob
AU - Mamven, Manmak
AU - Matekole, Michael
AU - Amodu, Olukemi
AU - Cooper, Richard
AU - Antwi, Sampson
AU - Adeyemo, Adebowale A.
AU - Ilori, Titilayo O.
AU - Adabayeri, Victoria
AU - Nyarko, Alexander
AU - Ghansah, Anita
AU - Amira, Toyin
AU - Solarin, Adaobi
AU - Awobusuyi, Olugbenga
AU - Kimmel, Paul L.
AU - Brosius, Frank Chip
AU - Makusidi, Muhammad
AU - Odenigbo, Uzoma
AU - Kretzler, Matthias
AU - Hodgin, Jeffrey B.
AU - Pollak, Martin R.
AU - Boima, Vincent
AU - Freedman, Barry I.
AU - Palmer, Nicholette D.
AU - Collins, Bernard
AU - Phadnis, Milind
AU - Smith, Jill
AU - Agwai, Celia I.
AU - Okoye, Ogochukwu
AU - Abdu, Aliyu
AU - Wilson, Jillian
AU - Williams, Winfred
AU - Salako, Babatunde L.
AU - Parekh, Rulan S.
AU - Tayo, Bamidele
AU - Adu, Dwomoa
AU - Ojo, Akinlolu
N1 - Publisher Copyright:
Copyright © 2024 Massachusetts Medical Society.
PY - 2025/1/16
Y1 - 2025/1/16
N2 - 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.).
AB - 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.).
UR - http://www.scopus.com/inward/record.url?scp=85216036665&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa2404211
DO - 10.1056/NEJMoa2404211
M3 - Article
C2 - 39465900
AN - SCOPUS:85216036665
SN - 0028-4793
VL - 392
SP - 228
EP - 238
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 3
ER -