In this study, we sought to evaluate the risk of the APOL1 genetic variants in patients with non-diabetic CKD (cases) and those at risk of CKD with normal kidney function (controls) in the Cameroonian population. The frequencies of the two risk alleles were two-fold higher amongst cases (29%) compared to the controls (13.9%), and for the recessive model of inheritance, the odds of having the two APOL1 genetic variants was 2,5 folds in cases compared to controls (p = 0.016; OR = 2.53). The odds were even higher for the APOL1 G1 risk allele in the recessive model of inheritance (p = 0.007; OR 3.91).
These results were similar to that found in the neighbouring Nigeria by Ulasi et al who reported a prevalence of the 2 APOL1 risk alleles 66% in the CKD population, with an associated increased odds for non-diabetic CKD (OR = 4,8; p = 5.1E-03). Tayo et al also reported this increased odds for CKD with APOL1 risk variants in the dominant, additive and recessive model of inheritance.
There was an even greater odds (almost 4-fold) for non-diabetic CKD with the G1 risk allele in the recessive model of inheritance which is similar to the findings of Tayo et al (OR = 3.8; p = 0.041). The AASK study reported increased risk for hypertensive nephropathy with the APOL1 variants and also showed the stronger association for the G1 allele . Similar findings were also reported for FSGS and HIVAN with APOL risk variants regardless of the mode of inheritance.
Kabore et al recently reported that the prevalence of the APOL1 genetic variants were lower in Senegal and Burkina Faso than previously reported in other west African countries with a prevalence of 13.3% amongst people living with HIV[8, 11]. Furthermore, they did not find an increased risk for declining kidney function in the CKD participants with the high risk APOL1 genetic variants. This could be because of their limited sample size as the number of high risk carriers amongst the CKD population were few.
It is believed that the APOL1 genetic variants protect their carriers from developing sleeping sickness caused by the Trypanosoma brucei rhodesiense, which explains the decreased prevalence of the disease in the western parts of Africa today. Africa has experienced 3 major epidemics of Trypanosomiasis in the last century with Cameroon being attacked during the second episode in 1920 . Presently, Cameroon is not in the epidemiological zone of T.b.rhodesiense. However, the 1000 genomes project study found an 8% prevalence of the APOL1 2 risk allele frequency in the Cameroon population . In a matched case-control setting, our study brought these findings a leap ahead by identifying a disproportionately higher number of the APOL1 2-risk allele frequency amongst the non-diabetic CKD population than in non-diabetic non-CKD controls, suggesting its implication in non-diabetic CKD.
The prevalence of hypertension and CKD are rising in Africa and more specifically, in Cameroon. There is correlation between the prevalence of hypertension and the zones of APOL1 genetic risk variant distribution in Africa . It is no longer in doubt whether APOL1 risk variants are susceptibility factors to non-diabetic CKD as it has been reported across many studies and we have also shown the same results in the Cameroonian population. What remains yet to be established is a causal relationship between the APOL1 variants and non-diabetic CKD.
Furthermore, our findings portrayed a 36.7% prevalence of the APOL1 alleles in the control population, raising the question, if APOL1 genetic risk variants constitute a risk factor for hypertension and other cardiovascular diseases and could form the basis of another study. 13.9% of the control population also had the two-risk allele state. This suggests that another hit or factor (either genetic or environmental) is needed to actually cause chronic kidney disease.