Relation between G1 and G2 haplotypes in the APOL1 gene and progression of chronic kidney disease in children

• Grant number: 17/02285-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2017
• End date: December 31, 2017
• Field of knowledge: Biological Sciences - Biophysics - Cellular Biophysics
• Principal Investigator: João Bosco Pesquero
• Grantee: Fernanda Maria Serafim Casimiro
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Genetic variations in the APOL1 gene that is located on chromosome 22, among other alterations, are associated with increased susceptibility to renal disease (DR) and may be related to the severity and progression of the disease, leading to a chronic condition. Previous studies have shown that individuals with African ancestry have polymorphisms in the APOL1 gene and have a higher prevalence of chronic kidney disease (CKD) when compared to European individuals. Changes in APOL1 protein may be considered high or low risk for developing kidney disease. The G1 haplotype is characterized by the exchange of two amino acids in the APOL1 protein (S342G and I384M). G2 is characterized by the deletion of 6 base pairs, in which two amino acids (N388 and Y389) are removed from the protein. Changes in homozygosity for G1 or G2 haplotypes or with both altered alleles (G1 and G2) are considered high risk (HR) changes for DR development. In contrast, changes in heterozygosis for G1 or G2, with only one altered allele, are considered low risk (LR) changes for DR development. Both haplotypes are plausible candidates for causal changes because they alter the sequence for protein coding. Thus, this study aims to evaluate the relationship between G1 and G2 haplotypes in the APOL1 gene and the progression of Chronic Kidney Disease in children with a diagnosis of CKD. To this end we intend to seek association between the presence of changes G1 and G2 in the APOL1 gene and time of evolution for end-stage renal disease in a group of 300 children diagnosed with CKD in a renal transplant service. For this, the analysis of exon 7 of the APOL1 gene will be performed and compared with the prognosis of children with CKD, finally evaluating whether polymorphisms in APOL1 are associated with the rate of development of the disease. (AU)