title: APOL1 genetic variants, chronic kidney diseases and hypertension in mixed ancestry South Africans.
abstract: BACKGROUND
  The 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Although 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.
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Wellness Science, Cape Peninsula University of Technology, PO Box 1906, Bellville, Cape Town, 7530, South Africa. matshat@cput.ac.za.
authors.forename: Tandi E
authors.initials: TE
authors.lastname: Matsha
authors.affiliation: Non-Communicable Diseases Research Unit, South African Medical Research Council & University of Cape Town, Cape Town, South Africa. apkengne@yahoo.com.
authors.forename: Andre P
authors.initials: AP
authors.lastname: Kengne
authors.affiliation: Department of Surgery, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa. kmasconi@gmail.com.
authors.forename: Katya L
authors.initials: KL
authors.lastname: Masconi
authors.affiliation: Department of Surgery, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa. Yandiswa.Yako@wits.ac.za.
authors.forename: Yandiswa Y
authors.initials: YY
authors.lastname: Yako
authors.affiliation: Division of Chemical Pathology, Faculty of Health Sciences, National Health Laboratory Service (NHLS) and University of Stellenbosch, Cape Town, South Africa. erasmusrajiv@gmail.com.
authors.forename: Rajiv T
authors.initials: RT
authors.lastname: Erasmus
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D015897:Comorbidity; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology* / Q000235:genetics*; D008075:Lipoproteins, HDL / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology* / Q000235:genetics*; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL