Abstract:
Chronic Kidney disease (CKD) is a global public health threat with higher incidence in African populations that is partially associated with SNP variants in MYH9 and APOL1 genes. Studies suggests that haemoglobin variants including Hb S and C play a role in CKD pathogenesis. The study aimed to investigate the associations between Hb S, C genotypes, APOL1 and MYH9 variants in CKD and their possible interactions to modifying the risk of CKD. Four SNPs, each in MYH9 and APOL1 (representing G1 and G2) Hb S and C were genotyped in 537 samples (260 cases-CKD of unknown aetiology and sickle cell nephropathy, 270 controls - healthy individuals and SCD without nephropathy) selected from archived H3Africa Kidney disease Research Network samples. Using chi squared test and logistic regression, the association and strength of association between each SNP and CKD was estimated, adjusting for gender, age and clinical site. Hb S was associated with about 2-9 folds increased risk of developing nephropathy (p-value ˂ 0.02). APOL1 G1 variant rs73885319 conferred between 30-70% increased risk of developing CKD of unknown aetiology (p-value ≤ 0.01). In a recessive and heterozygote model, MYH9 variant rs4821481 increased the risk of developing nephropathy in SCD by 2-4 folds (OR=1.99 and 4.44 respectively, p-value ˂ 0.01). There was a synergistic epistatic interaction between Hb AS genotype and APOL1 rs73885319 resulting in a further increased risk (130%) of CKD for heterozygote APOL1 rs73885319 individuals who are Hb S carriers. Results of the study though preliminary, will inform public health decisions on screening of new-borns for SCD, SCT and other common genetic predispositions of CKD.
