“This is the most extensive collaborative research on epidemiology and genetics of CKD and FSGS from Africa. These findings are significant for public health, given the high prevalence of APOL1 CKD variants in Africans.”
Focal segmental glomerulosclerosis (FSGS) and other chronic kidney diseases (CKDs) are leading causes of morbidity and mortality in the US and around the world. People of African ancestry are disproportionately more affected due to structural racism, disparity in care, implicit bias, and biological and genetic factors. Variants in the APOL1 gene (G1 and G2) were reported in 2010 as major genetic factors driving this disparity. Previous research showed that having two copies of the variants in different combinations (G1/G1, G1/G2, G2/G2) increases the risk of FSGS by about 17-fold and CKD by about two-fold in African Americans, but the role of having just one copy of the APOL1 variant was unknown.
In the first population-based study from Africa, the H3Africa Kidney Disease Research Network (H3Africa KDRN) recruited over 8,000 people from more than ten academic medical centers in Ghana and Nigeria, including nearly 5,000 people with CKD stages 2-5 and kidney biopsy confirmed FSGS and other diseases of the kidney filters, to investigate the role of having one or two copies of the APOL1 variants. Their results were presented at ASN Kidney Week 2024 with simultaneous publication in the New England Journal of Medicine.
The study found that having just one risk variant in the APOL1 gene can significantly increase the risk of developing CKD and FSGS in Africans living in West Africa. The researchers also reported that in some populations in Nigeria and Ghana, the prevalence of two copies of the variants (G1/G1, G1/G2, G2/G2) could be as high as 30-50% compared with 13% reported in African Americans.
The G1 and G2 variants in the APOL1 gene likely helped combat two forms of African sleeping sickness thousands of years ago. But now, even having one of these variants in one copy of the APOL1 gene increases the risk of developing CKD. Their results show that having one risk variant increases the risk of CKD and FSGS by 18% and 61%, respectively. This updates previous findings suggesting that a person needed two copies of APOL1 gene variants to increase the overall risk of CKD and FSGS.
“This is the most extensive collaborative research on epidemiology and genetics of CKD and FSGS from Africa,” said lead author Rasheed Gbadegesin, Wilburt C. Davison Distinguished Professor of Pediatrics at Duke University School of Medicine and Co-Chair of ISGD's Basic and Translational Research Committee. “These findings are significant for public health, given the high prevalence of APOL1 CKD variants in Africans.”
With this research, Gbadegesin and team define the role of APOL1 variants in CKD in Africans living in Africa and show the prevalence of APOL1 high-risk genotype could be as high as 50% in some populations in Africa. This dramatically increases the pool of patients with APOL1-associated kidney disease, which may make this group a target for future clinical trials that are likely to significantly reduce the disparity in the severity and prevalence of CKD in Africans all over the World.
Next, the H3Africa KDRN will replicate the findings from this study in other African populations, use these findings to set the stage for clinical trials of compounds targeting APOL1 in Africa, and conduct additional studies to define the genetic architecture of CKD in Africa comprehensively.
The H3Africa consortium, an initiative of the NIH and Wellcome Trust UK, has the broad goals of 1) Defining the genetic architecture of CKD and other diseases in Africa, 2) Establishing infrastructure for genomics Research in Africa, and 3) Building capacity for genomic research in Africa.
References:
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; H3Africa Kidney Disease Research Network. APOL1 Bi- and Monoallelic Variants and Chronic Kidney Disease in West Africans. N Engl J Med. 2024 Oct 26. doi: 10.1056/NEJMoa2404211. Epub ahead of print. PMID: 39465900.
COMMENTS