APOL1 Kidney Disease Variants — Information from West Africa at Last

Background:

Chronic kidney disease (CKD) disproportionately affects populations of African ancestry, particularly in West Africa, where it often progresses rapidly. Focal segmental glomerulosclerosis (FSGS), an aggressive cause of CKD, is highly prevalent among people of African descent. Two variants in APOL1, G1 and G2, are associated with increased susceptibility to FSGS and other forms of CKD. These variants evolved due to positive selection for protection against Trypanosoma brucei but confer a higher risk of kidney disease in homozygous or compound heterozygous individuals.

Methods:

The study by Ghadegesin et al. analyzed APOL1 genotyping among 8,355 participants from Ghana and Nigeria, including 4,712 with CKD stages 2–5, 866 with biopsy-proven glomerular diseases, and 2,777 controls. The prevalence of APOL1 recessive risk genotypes was assessed across ethnolinguistic groups.

Results:

Biallelic APOL1 variants (G1/G1, G2/G2, or G1/G2) were associated with increased odds of CKD (adjusted odds ratio [OR], 1.25) and FSGS (OR, 1.84), though the effect size was smaller than in African diaspora populations. Monoallelic carriers (G0/G1 or G0/G2) also showed elevated risks (CKD OR, 1.18; FSGS OR, 1.61). The G2 variant drove most of the kidney disease risk signal.

Conclusion:

The study provides a large-scale view of APOL1 variants in West Africa, highlighting lower-than-expected effect sizes, potential survival biases, and confounding factors like infectious or environmental risks. Comprehensive genome sequencing and environmental analyses are needed to advance precision medicine for APOL1-related kidney disease.

Background:

Chronic kidney disease (CKD) disproportionately affects populations of African ancestry, particularly in West Africa, where it often progresses rapidly. Focal segmental glomerulosclerosis (FSGS), an aggressive cause of CKD, is highly prevalent among people of African descent. Two variants in APOL1, G1 and G2, are associated with increased susceptibility to FSGS and other forms of CKD. These variants evolved due to positive selection for protection against Trypanosoma brucei but confer a higher risk of kidney disease in homozygous or compound heterozygous individuals.

Methods:

The study by Ghadegesin et al. analyzed APOL1 genotyping among 8,355 participants from Ghana and Nigeria, including 4,712 with CKD stages 2–5, 866 with biopsy-proven glomerular diseases, and 2,777 controls. The prevalence of APOL1 recessive risk genotypes was assessed across ethnolinguistic groups.

Results:

Biallelic APOL1 variants (G1/G1, G2/G2, or G1/G2) were associated with increased odds of CKD (adjusted odds ratio [OR], 1.25) and FSGS (OR, 1.84), though the effect size was smaller than in African diaspora populations. Monoallelic carriers (G0/G1 or G0/G2) also showed elevated risks (CKD OR, 1.18; FSGS OR, 1.61). The G2 variant drove most of the kidney disease risk signal.

Conclusion:

The study provides a large-scale view of APOL1 variants in West Africa, highlighting lower-than-expected effect sizes, potential survival biases, and confounding factors like infectious or environmental risks. Comprehensive genome sequencing and environmental analyses are needed to advance precision medicine for APOL1-related kidney disease.