Kidney Disease Genetic Risk Common in West Africans

SAN DIEGO — APOL1 genotypes associated with high risk for chronic kidney disease (CKD) were common among individuals living in West Africa, suggesting a mechanism at play in the high rates of kidney disease in African Americans.

More than 40% of the Ghanaian and Nigerian individuals tested carried APOL1 variants linked to increased risk of chronic kidney disease, and the risk of kidney disease was “dose” dependent, Rasheed A. Gbadegesin, MBBS, MD, of Duke University Medical Center in Durham, North Carolina, reported at the American Society of Nephrology Kidney Week meeting. The results were published simultaneously in the New England Journal of Medicine.

One APOL1 G1 or G2 risk allele carried 18% higher odds of CKD and 61% higher odds of focal segmental glomerulosclerosis (FSGS) than no risk alleles. Carrying two risk alleles was associated with 25% higher odds of CKD and 84% higher odds of FSGS than with one or no risk alleles.

“There is obvious disparity in chronic kidney disease and FSGS in people of African ancestry,” Gbadegesin said at the late-breaking science session. “We have some ideas about what the drivers of these disparities are: structural racism, mistrust of the health system, disparity in care, implicit bias, and a lot of environmental factors. But there are actually biological genetic factors that are also important for this.”

The link between APOL1 and kidney disease has been recognized for more than a decade, but only a few population-based studies have assessed its prevalence (occurring in one in eight Black adults) and most were carried out in African diaspora populations, Gbadegesin noted. “And we know that since the mass exodus there’s been a lot of admixture.” West Africa is “a region that contributed substantially to the ancestry of Black Americans,” his group noted.

To look for the source of this mutation, Gbadegesin said his group decided to do a study in Africa.

Their H3Africa Kidney Disease Research Network performed a case-control study in West Africa (63.3% Nigerians and 36.7% Ghanaians) involving 4,712 participants who had chronic kidney disease stages 2 through 5, 866 with biopsy-proven glomerular disease, and 2,777 with no kidney disease.

Overall, 43.0% carried one APOL1 risk allele, considered a low-risk genotype; the 29.7% carrying two APOL1 risk alleles were considered high-risk genotypes.

However, the distribution of high-risk genotypes was not uniform across the two countries. Southeastern Nigeria had prevalence of high-risk genotypes of up to 50%, while southern Ghana had about a 35% rate as well. “This is in sharp contrast with the 13% that has been reported in the U.S.,” Gbadegesin said. Northern Nigeria had a prevalence of about 11%, “comparable with what we have in African Americans living in the U.S., and it seems as if this is actually driving a phenotype.”

Logistic-regression models controlled for covariates, including clinical site, age, and sex.

“The big thing that we find here is that the single APOL1 … risk alleles may also be associated with chronic kidney disease, probably acting in concert with other genetic modifiers or environmental factors,” Gbadegesin noted. Previous studies had been underpowered to look at the effect of single alleles.

He concluded that routine APOL1 genotyping is warranted in West Africans with chronic kidney disease. “There is a need for comprehensive study of genetic architecture of CKD in Africa,” he added.

The researchers noted that the study population was representative of the West African population affected by CKD, although perhaps not be generalizable to other populations.

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