APOL1 genetic variants, chronic kidney diseases and hypertension in mixed ancestry South Africans.

Tandi E Matsha,Katya L Masconi,Andre P Kengne,Rajiv T Erasmus,Yandiswa Y Yako

doi:10.1186/s12863-015-0228-6

Abstract

BackgroundThe frequencies of apolipoprotein L1 (APOL1) variants and their associations with chronic kidney disease (CKD) vary substantially in populations from Africa. Moreover, available studies have used very small sample sizes to provide reliable estimates of the frequencies of these variants in the general population. We determined the frequency of the two APOL1 risk alleles (G1 and G2) and investigated their association with renal traits in a relatively large sample of mixed-ancestry South Africans. APOL1 risk variants (G1: rs60910145 and rs73885319; G2: rs71785313) were genotyped in 859 African mixed ancestry individuals using allele-specific TaqMan technology. Glomerular filtration rate (eGFR) was estimated using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations.ResultsThe frequencies of rs73885319, rs60910145 and rs71785313 risk alleles were respectively, 3.6 %, 3.4 %, and 5.8 %, resulting in a 1.01 % frequency of the APOL1 two-risk allele (G1:G1 or G1:G2 or G2:G2). The presence of the two-risk allele increased serum creatinine with a corresponding reduction in eGFR (either MDRD or CKD-EPI based). In dominant and log-additive genetic models, significant associations were found between rs71785313 and systolic blood pressure (both p ≤ 0.025), with a significant statistical interaction by diabetes status, p = 0.022, reflecting a negative non-significant effect in nondiabetics and a positive effect in diabetics.ConclusionsAlthough the APOL1 variants are not common in the mixed ancestry population of South Africa, the study does provide an indication that APOL1 variants may play a role in conferring an increased risk for renal and cardiovascular risk in this population.

Highlights

The frequencies of apolipoprotein L1 (APOL1) variants and their associations with chronic kidney disease (CKD) vary substantially in populations from Africa
The eGFR was significantly lower in individuals with diabetes compared to those without diabetes as well as in women vs. men, whilst systolic blood pressure and diastolic blood pressure were significantly elevated in men
In participants with two-risk alleles, serum creatinine was elevated with a corresponding reduction of eGFR than in those with only one-risk allele or none, but differences did not reach statistical significance

Summary

Introduction

The frequencies of apolipoprotein L1 (APOL1) variants and their associations with chronic kidney disease (CKD) vary substantially in populations from Africa. In 2008, through admixture-mapping linkagedisequilibrium genome scan, two landmark studies identified a risk locus on chromosome 22q12.3 which explained the increased burden of nondiabetic endstage renal disease (ESRD) and focal segmental glomerulosclerosis (FSGS) in individuals of recent African ancestry [1, 2]. These studies provided evidence that genetic variation on the myosin gene (MYH9) conferred most or most of the increased risk for nondiabetic kidney disease in African Americans [1, 2]. We sought to determine the frequency of APOL1 variants and their association with CKD traits in a South African population with an African ancestry, high prevalence of CKD and poor cardiovascular risk profile

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Conclusion