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

Authors :: Gbadegesin RA
Ulasi I
Ajayi S
Raji Y
Olanrewaju T
Osafo C
Ademola AD
Asinobi A
Winkler CA
Burke D
Arogundade F
Ekem I
Plange-Rhule J
Mamven M
Matekole M
Amodu O
Cooper R
Antwi S
Adeyemo AA
Ilori TO
Adabayeri V
Nyarko A
Ghansah A
Amira T
Solarin A
Awobusuyi O
Kimmel PL
Brosius FC
Makusidi M
Odenigbo U
Kretzler M
Hodgin JB
Pollak MR
Boima V
Freedman BI
Palmer ND
Collins B
Phadnis M
Smith J
Agwai CI
Okoye O
Abdu A
Wilson J
Williams W
Salako BL
Parekh RS
Tayo B
Adu D
Ojo A
Source :: The New England journal of medicine [N Engl J Med] 2025 Jan 16; Vol. 392 (3), pp. 228-238. Date of Electronic Publication: 2024 Oct 26.
Publication Year :: 2025
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.<br />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.<br />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.<br />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.).<br /> (Copyright © 2024 Massachusetts Medical Society.)