title: A novel single-nucleotide substitution, Leu 467 Pro, in the interferon-gamma receptor 1 gene associated with allergic diseases.
abstract: We identified a novel heterozygous single-nucleotide substitution 1400 T right curved arrow C (Leu 467 Pro) in the seventh exon of the interferon-gamma receptor 1 (IFNGR1) gene. This substitution was detected in 6 of the 89 allergic patients but not in the 72 non-allergic subjects. There was a difference in the L467P frequency between the allergic patients and the non-allergic subjects (Fisher's exact test: p=0.033). The 6 patients with L467P have allergic diseases such as bronchial asthma and/or allergic rhinitis. Furthermore, a familial analysis for L467P revealed a linkage between allergic diseases and L467P. Serum IgE levels of the patients with L467P were higher than those of the non-allergic subjects (p=0.001). Our previous studies have been shown that interferon-gamma (IFN-gamma) production by PBMCs in the allergic patients was lower than that in the non-allergic subjects. In this study, although IFN-gamma production in the allergic patients with L467P was equivalent to that in the non-allergic subjects, their serum IgE levels were high and they had allergic diseases. Our results suggest that some allergic patients have IFNGR dysfunction, and that L467P in the IFNGR1 gene is one of candidate susceptibility genes for allergic diseases.
authors.affiliation: Department of Pediatrics, Gifu University School of Medicine, Gifu 500-8705, Japan. e2104001@guedu.cc.gifu-u.ac.jp
authors.forename: Minako
authors.initials: M
authors.lastname: Aoki
authors.forename: Eiko
authors.initials: E
authors.lastname: Matsui
authors.forename: Hideo
authors.initials: H
authors.lastname: Kaneko
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Inoue
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukao
authors.forename: Mizuho
authors.initials: M
authors.lastname: Watanabe
authors.forename: Takahide
authors.initials: T
authors.lastname: Teramoto
authors.forename: Zenichiro
authors.initials: Z
authors.lastname: Kato
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Suzuki
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Kimiko
authors.initials: K
authors.lastname: Kasahara
authors.forename: Naomi
authors.initials: N
authors.lastname: Kondo
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D001249:Asthma / Q000235:genetics; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D004268:DNA-Binding Proteins / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics*; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology; D020382:Interleukin-18 / Q000494:pharmacology; D007930:Leucine / Q000235:genetics; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010375:Pedigree; D010766:Phosphorylation; D017354:Point Mutation; D011392:Proline / Q000235:genetics; D017471:Receptors, Interferon / Q000235:genetics*; D012221:Rhinitis, Allergic, Perennial / Q000235:genetics; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D000096743:Interferon gamma Receptor
chemical_list: D004268:DNA-Binding Proteins; D007073:Immunoglobulin E; D007371:Interferon-gamma; D018664:Interleukin-12; D020382:Interleukin-18; D007930:Leucine; D011392:Proline; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D000096743:Interferon gamma Receptor; C494079:STAT1 protein, human