title: Functional polymorphism in the suppressor of cytokine signaling 1 gene associated with adult asthma.
abstract: Suppressor of cytokine signaling (SOCS) 1 is an essential physiologic regulator of the IFN-gamma signaling that is crucial to lead appropriate immune responses, and impaired IFN-gamma production is considered a hallmark of atopic diseases. Recent study has shown that SOCS1 is also crucial in attenuating type 1 IFN signaling and in limiting the host response to viral infection. Clinical and experimental evidence suggest an important role for respiratory viral infections in the development of asthma. To assess genetic functional variants of SOCS1 related to susceptibility and clinical phenotypes in adult asthma in a Japanese population, we conducted association and haplotype analyses of 462 subjects with adult asthma and 639 control subjects. After screening for polymorphisms, we identified a total of 13 variants and characterized the linkage disequilibrium (LD) mapping of the gene. Three variants were selected for genotyping with regard to the LD pattern, and we found a significant association between an SOCS1 promoter polymorphism -1478CA > del and adult asthma (P = 0.0063). The three-locus haplotype of SOCS1 using these three polymorphisms also showed a positive association with a haplotype T-C-del (-5388T, -3969C, and -1478 del; P = 0.0097). Furthermore, reporter gene analysis revealed that related promoter variant -1478 del enhanced the transcriptional level of SOCS1 in human lung epithelial cells, and induced higher levels of protein expression of SOCS1 and lower phosphorylation of STAT1 stimulated with IFN-beta. These findings suggest that the SOCS1 gene might be involved in the development of adult asthma through functional genetic polymorphism.
authors.affiliation: Laboratory for Genetics of Allergic Diseases, SNP Research Center, Institute of Physical and Chemical Research (RIKEN), 1-7-22 Suehiro, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Michishige
authors.initials: M
authors.lastname: Harada
authors.forename: Kazuko
authors.initials: K
authors.lastname: Nakashima
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Hirota
authors.forename: Makiko
authors.initials: M
authors.lastname: Shimizu
authors.forename: Satoru
authors.initials: S
authors.lastname: Doi
authors.forename: Kimie
authors.initials: K
authors.lastname: Fujita
authors.forename: Taro
authors.initials: T
authors.lastname: Shirakawa
authors.forename: Tadao
authors.initials: T
authors.lastname: Enomoto
authors.forename: Mamoru
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Moriyama
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Saito
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tamari
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000235:genetics*; D002874:Chromosome Mapping; D004198:Disease Susceptibility; D005260:Female; D005787:Gene Frequency; D017930:Genes, Reporter; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*; D014162:Transfection
chemical_list: C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins