FCGR2A single nucleotide polymorphism confers susceptibility to childhood-onset idiopathic nephrotic syndrome.

Childhood-onset idiopathic nephrotic syndrome affects 1.15–3.4 children/100,000 children/year in Western Countries. Immune-mediated mechanisms, particularly T cell-mediated, are thought to play a key pathogenic role. The genetic basis of the disease is still poorly understood. We tested the association between single nucleotide polymorphisms (SNPs) of four genes encoding Fc gamma receptors ( FCGR2A , FCGR2B , FCGR3A , FCGR3B ) and idiopathic nephrotic syndrome in a case-control study of paediatric patients. Children with idiopathic nephrotic syndrome (aged 1–16 years) were included. FCGR2A rs1801274 and FCGR3A rs396991 SNPs were genotyped using real-time PCR with the TaqMan method, while FCGR2B rs1050501 and FCGR3B NA1/NA2 were genotyped using Sanger sequencing. Fisher’s exact test was used to explore genetic association. We enrolled 103 idiopathic nephrotic syndrome patients and 181 healthy controls. A significant association was found between idiopathic nephrotic syndrome and FCGR2A rs1801274 SNP (both with the T allele and the TT genotype, p value = 0.0009, OR 1.81, 95% CI 1.27–2.59 and p value = 0.0007, OR 2.39, 95% CI 1.44–3.99, respectively). No associations were found for the remaining SNPs. Fc gamma receptors might modulate response to rituximab; since 60 of the enrolled patients were treated with rituximab, we also tested the association between the studied SNPs and rituximab efficacy in this patient subgroup, but found only a weak association with FCGR2A CC genotype (p value = 0.03). The FCGR2A rs1801274 SNP in the gene encoding the activating receptor CD32A confers susceptibility to idiopathic nephrotic syndrome. [ABSTRACT FROM AUTHOR]