<i>APOL1</i> Bi- and Monoallelic Variants and Chronic Kidney Disease in West Africans.

Abstract

Apolipoprotein L1 gene (<i>APOL1</i>) 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 <i>APOL1</i> variants with CKD in West Africans, a major group in the Black population. 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 <i>APOL1</i> variants among participants with high-risk genotypes (two <i>APOL1</i> risk alleles) and those with low-risk genotypes (fewer than two <i>APOL1</i> risk alleles) by fitting logistic-regression models that controlled for covariates, including clinical site, age, and sex. Among 8355 participants (4712 with CKD stages 2 through 5, 866 with glomerular diseases, and 2777 with no kidney disease), the prevalence of monoallelic <i>APOL1</i> variants was 43.0% and that of biallelic <i>APOL1</i> variants was 29.7%. Participants with two <i>APOL1</i> 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 <i>APOL1</i> 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 <i>APOL1</i> variants with CKD or focal segmental glomerulosclerosis. In this study, monoallelic <i>APOL1</i> variants were associated with 18% higher odds of CKD and 61% higher odds of focal segmental glomerulosclerosis; biallelic <i>APOL1</i> 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.).