Polymorphism in promoter region of Fcα receptor gene in patients with IgA nephropathy

Abstract

We have recently identified two novel polymorphisms (-114T/C and +56T/C relative to the major transcription start site) in the functional promoter region of the Fcalpha receptor (FcalphaR) gene. Since altered FcalphaR expression may be associated with IgA nephropathy, we examined these promoter polymorphisms in this disease. Patients with IgA nephropathy (n = 90), patients with other primary glomerulonephritis (n = 50), and healthy adults (n = 83) were studied. Genotyping was performed by the polymerase chain reaction (PCR) followed by direct sequence analysis and was subsequently confirmed by PCR with mismatched primers followed by restriction fragment length polymorphism analysis. The study demonstrated that the frequency of the +56C allele in patients with IgA nephropathy (0.511) was significantly (P < 0.01) higher than that in patients with other primary glomerulonephritis (0.350) and healthy adults (0.337). In addition, a significant increase in the frequency of the +56CC genotype was observed in patients with IgA nephropathy (27.8% vs 10.0% in other GN and vs 9.6% in healthy adults). In contrast, no significant difference in the frequencies of the +56CC genotype and +56C allele was observed between other primary glomerulonephritis patients and healthy adults. The frequency of the -114CC genotype in patients with IgA nephropathy was significantly increased compared with those in both control groups (15.6% vs 4.0% in other GN and vs 2.4% in healthy adults). Polymorphisms of the FcalphaR promoter region therefore appear to be associated with susceptibility to IgA nephropathy, suggesting the importance of the FcalphaR gene and its expression in this disease.

Genetic polymorphisms in the promoter and 5′ UTR region of the Fc α receptor (CD89) are not associated with a risk of IgA nephropathy

“…It is possible that our study population was not large enough to produce statistically significant results. Nonetheless, the numbers of patients with IgAN and with other types of glomerulonephritis analyzed in this study were much larger than a previous report that showed a significant difference between the genotype and allele distributions of the two groups (Tsuge et al 2001). The number of subjects with IgAN was 151 in the present study, but only 90 in the previous study.…”

Pre-Existing Glomerular Immune Complexes Induce Polymorphonuclear Cell Recruitment Through an Fc Receptor-Dependent Respiratory Burst: Potential Role in the Perpetuation of Immune Nephritis

“…Growing evidence has shown that genetic polymorphisms of FcR and consequent alteration of their function may affect the prognosis of these IC diseases (1)(2)(3). In the last decade experimental studies, particularly with different knockout strains of animals, have revealed that FcR are crucial molecules providing a critical link between ligands (IC) and effector cells in IC-mediated inflammatory cascade (4,5).…”

C/EBPα and Ets Protein Family Members Regulate the Human Myeloid IgA Fc Receptor (FcαR, CD89) Promoter

“…To analyze in detail the cell type specificity of this region, 5Ј and 3Ј truncation mutants were fused to the firefly luciferase gene and transfected into various cell lines. In our previous papers (11,12), we numbered nucleotide positions from the major transcription site that had been identified by de Wit et al (20). However, since the Fc␣R promoter appears to contain multiple transcription start sites (20) (our unpublished observations), we hereafter designate the ATG translation initiation codon as ϩ1.…”