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

Abstract

The molecular mechanisms of immunoglobulin A glomerulonephritis (IgAN), the most prevalent form of primary glomerulonephritis, remain poorly understood. Recently, the essential role of soluble Fc α receptor (FcαR) in the formation of the pathogenic immune complex has been revealed. We screened genomic DNA samples from patients with IgAN and those with other glomerular diseases for polymorphisms in the promoter and the 5Ј-untranslated region region of the FcαR gene by direct nucleotide sequencing. We found three common polymorphisms in this region, T-114C, T-27C, and Tϩ56C from the putative transcription initiation site. Each genotype was determined in 151 patients with IgAN and 163 patients with other glomerular diseases shown to have no mesangial IgA deposition by renal biopsy. The haplotype analysis revealed tight linkage disequilibrium among them. An association study for the genotype, allele, and haplotype frequencies of the polymorphisms between the patients with histologically proven IgAN and those with other glomerular diseases showed no significant difference in the genotype, allele, and haplotype distributions between the two groups. The present study indicates that the analyzed polymorphisms of the FcαR gene do not appear to be primarily involved in the susceptibility to IgAN.

Association of Megsin2093C/T, 2180C/TandC25663Ggene polymorphism with the risk of IgA nephropathy

“…1 IgAN is responsible for approximately 20% of the patients reaching end-stage renal diseases (ESRD). 2 Furthermore, IgAN has a variable clinical course, 3 poor prognostic factors include hypertension, severe proteinuria, and histological appearance of the renal biopsy specimen.…”

Are Single Nucleotide Polymorphisms of the <i>Immunoglobulin A Fc Receptor</i> Gene Associated with Allergic Asthma?

“…In summary, although our results do not show any association of FCAR gene polymorphisms with allergic asthma, we present here two novel polymorphisms in this gene that may prove valuable in studies on its association with other diseases, such as IgA nephropathy [21, 22, 34]and ankylosing spondylitis [35]. In addition, we describe here, for the first time, the distributions of the FCAR promoter, EC1, and C tail polymorphisms in Caucasians.…”

“…1b). Sequencing revealed a –142T/C variation, already described in Japanese people [13, 21, 22]. Lane 2 shows a typical four-band pattern (from bottom to top: homoduplexes –142CG and –142TA and heteroduplexes –142CA and –142TG).…”

“…1a), suggesting two different SNPs. Indeed, the sequencing revealed an SNP, the –311T/C variation, described so far only in Japanese people [13, 21, 22], and, in addition, a novel SNP (G/A), not described so far, was found at position –340 (submitted to the HGVbase as SNP002901726). Three different homozygotes giving single homoduplex bands are shown: lane 1, –340GG, –311TT; lane 3, –340GG, –311CC, and lane 5, –340AA, –311CC.…”

“…Association of the –311C/T and –142C/T variants of the FCAR gene with another disease, IgA nephropathy, is still controversial: it was found in Japanese people by Tsuge et al [21], but not by Narita et al [22]. When the distributions of the –311T and –311C as well as the –142T and –142C alleles in our population are compared with those described in the Japanese population [13, 21, 22], we see that at both sites the T and C alleles are more evenly distributed than in Japanese people, where the T alleles, giving lower gene expression, are much more frequent than the C alleles.…”