Study reveals risk factors for pediatric primary focal segmental glomerulosclerosis
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Researchers identified functionally relevant risk factors for pediatric primary focal segmental glomerulosclerosis in African American children, according to data published in the American Journal of Kidney Diseases.
“The genetic bases for pediatric primary focal segmental glomerulosclerosis (FSGS), as opposed to familial FSGS, have not been widely investigated beyond apolipoprotein L1. Because of the strong association of FSGS with kidney failure, it is essential to further characterize the molecular determinants of this disease in order to improve the pathogenesis understanding and clinical outcomes for patients,” Axelle Durand, MSc, from Nantes Université in France, and colleagues wrote.
In a prospective cohort with case-control genetic association study, researchers examined 140 African American children with chronic kidney disease from the CKD in Children cohort. Of the population, there were 32 children with FSGS who researchers compared with the 108 children with non-FSGS CKD.
With primary biopsy proven pediatric FSGS serving as the primary outcome, researchers considered single nucleotide polymorphisms (SNP) the predictors. Researchers tested 680,138 SNPs for correlation and conducted a pathway enrichment analysis in addition to a human leucocyte antigen (HLA)-focused association study.
Overall, 169 SNPs from 14 independent loci correlated with FSGS. Researchers identified signals for genetic variants with the APOL1, Alstrom syndrome 1 (ALMS1) and fibroblast growth factor receptor 4 genes which had been previously connected to adult FSGS, kidney function or CKD. Moreover, growth factor receptor-bound protein 2 (GRB2) and integrin beta 1 (ITGB1) were reported as novel functionally relevant genes.
Ultimately, researchers demonstrated the importance of immune responses and antigen presentation in pediatric FSGS through SNP correlations within protein tyrosine phosphatase receptor type J that plays a role in T-cell receptor signaling.
“To conclude, our genomic association study of primary FSGS in African American children has revealed 14 independent significant loci, involving biologically relevant genes. These include APOL1 and ALMS1 that were previously associated with adult FSGS, GRB2 that promotes the podocyte slit diaphragm maintenance, and CDH12 and ITGB1 that were previously linked to kidney injury. We also provided evidence for a major role for immune responses and class II HLA molecules in pediatric FSGS. Collectively, these results contribute to better depicting the molecular pathophysiological pathways in pediatric idiopathic FSGS.”
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