The α‐chain of high‐affinity receptor for IgE (FcɛRIα) gene polymorphisms and serum IgE levels

Abstract

Our findings of genotype-related differences in IgE levels in allergic patients suggest an impact of -344 C>T but not -95 T>C gene polymorphism of FcepsilonRIalpha on total levels of IgE. The genetic variability in FcepsilonRIalpha at the -344 nucleotide of its regulatory sequence, though not related to atopy, predicts higher levels of the immunoglobulin.

Two Different Transcription Factors Discriminate the −315C>T Polymorphism of theFcεRIα Gene: Binding of Sp1 to −315C and of a High Mobility Group-Related Molecule to −315T

“…The necessity of the ␣-chain in IgE-mediated allergic reactions was definitively proved by the abolishment of anaphylaxis in ␣-chain-deficient mice (1). Recently, several groups including us reported studies regarding the association of Ϫ315 and Ϫ66 SNPs in the ␣-chain promoter with allergic diseases (2)(3)(4)(5). In the present study, we analyzed the role of these SNPs in the function of the ␣-chain promoter and found that the Ϫ315C and Ϫ315T sequences are recognized by two different transcription factors, as summarized in Fig.…”

“…Recently, two independent groups reported that an SNP at Ϫ315 (Ϫ344) but not Ϫ66 (Ϫ95) is associated with IgE levels in allergic patients with asthma or urticaria (4), or IgE levels in aspirin-intolerant chronic urticaria (5). Interestingly, these two SNPs at Ϫ315 and Ϫ66 were not judged to be in LD in one report (5), whereas they were concluded to be in complete LD in another one (4,17). The latter study showed allele frequency including both SNPs; in brief, Ϫ315T/Ϫ66T is the most common, the two haplotype variants Ϫ315C/Ϫ66T and Ϫ315C/Ϫ66C occur with similar frequency, and Ϫ315T/Ϫ66C is absent in Polish population (4,17).…”

“…Interestingly, these two SNPs at Ϫ315 and Ϫ66 were not judged to be in LD in one report (5), whereas they were concluded to be in complete LD in another one (4,17). The latter study showed allele frequency including both SNPs; in brief, Ϫ315T/Ϫ66T is the most common, the two haplotype variants Ϫ315C/Ϫ66T and Ϫ315C/Ϫ66C occur with similar frequency, and Ϫ315T/Ϫ66C is absent in Polish population (4,17). If the two SNPs are linked to each other, the result of comparison between Ϫ315T and Ϫ315C may be partly influenced by Ϫ66 SNP.…”

“…However, the relationship between Ϫ315 and Ϫ66 SNP is controversial, which may reflect statistical interdependence. In brief, Ϫ315 and Ϫ66 SNPs were described to be in complete linkage disequilibrium (LD) in one report (4) but not in LD in another one (5). Therefore, in the present study, we determined the genotypes of Ϫ315 and Ϫ66 in the Japanese population to examine the relationship of the two SNPs.…”

“…Recently, two single nucleotide polymorphisms (SNPs) 4 in the human ␣-chain promoter, Ϫ315CϾT and Ϫ66TϾC, have been shown to be associated with allergic diseases (we number nucleotides based on the transcription start site being expressed as ϩ 1 according to the genetic rule; although, in some studies, these nucleotides have been numbered Ϫ344 or Ϫ335 and Ϫ95 using the translation start site as ϩ 1) (2-5). We previously analyzed the effect of a Ϫ66TϾC SNP on the function of the ␣-chain gene and found that the occurrence of an additional GATA-motif in the Ϫ66T allele resulted in higher affinity to GATA-1, which subsequently caused higher transactivation of the promoter (2).…”