title: The GSTP1 gene is a susceptibility gene for childhood asthma and the GSTM1 gene is a modifier of the GSTP1 gene.
abstract: BACKGROUND
  Bronchial asthma is a chronic airway disorder characterized by bronchial inflammation. Oxidative stress is a key component of inflammation. Glutathione S-transferase P1 (GSTP1), the abundant isoform of glutathione S-transferases (GSTs) in lung epithelium, plays a key role in cellular protection against oxidative stress. Several studies have shown that the GSTP1 geneis involved in the pathogenesis of asthma and a gene-gene interaction may occur within the GST gene superfamily.
  
  
  METHODS
  We screened single-nucleotide polymorphisms (SNPs) at the GSTP1 locus and performed an association study in the Japanese population using two independent case-control groups (group 1: 391 pediatric patients with asthma, 462 adult patients with asthma, and 639 controls, and group 2: 115 pediatric patients with asthma and 184 controls). The effect of GSTM1 null/present genotype on the association between GSTP1 Ile105Val and asthma was also investigated.
  
  
  RESULTS
  We identified 20 SNPs at this locus and found this region consisted of one linkage disequilibrium block represented by four SNPs (tag SNPs). The association between the Ile105Val polymorphism in the GSTP1 gene and childhood asthma was significant in both groups (p = 0.047 in group 1, and p = 0.021 in group 2). This association was only significant in patients with GSTM1-positive genotype in both groups (group 1: GSTM1 present p = 0.013 and GSTM1 null p = 0.925, and group 2: GSTM1 present p = 0.015 and GSTM1 null p = 0.362).
  
  
  CONCLUSIONS
  These findings suggest that the GSTP1 gene is a childhood asthma susceptible gene, and the GSTM1 gene is a modifier gene of GSTP1 for the risk of childhood asthma in the Japanese population.
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Kamada
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Mashimo
authors.forename: Hiroki
authors.initials: H
authors.lastname: Inoue
authors.forename: Chenchen
authors.initials: C
authors.lastname: Shao
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Hirota
authors.forename: Satoru
authors.initials: S
authors.lastname: Doi
authors.forename: Makoto
authors.initials: M
authors.lastname: Kameda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Kimie
authors.initials: K
authors.lastname: Fujita
authors.forename: Tadao
authors.initials: T
authors.lastname: Enomoto
authors.forename: Sei
authors.initials: S
authors.lastname: Sasaki
authors.forename: Hiroko
authors.initials: H
authors.lastname: Endo
authors.forename: Reiko
authors.initials: R
authors.lastname: Takayanagi
authors.forename: Chifuyu
authors.initials: C
authors.lastname: Nakazawa
authors.forename: Toshio
authors.initials: T
authors.lastname: Morikawa
authors.forename: Miki
authors.initials: M
authors.lastname: Morikawa
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Miyabayashi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Chiba
authors.forename: Gen
authors.initials: G
authors.lastname: Tamura
authors.forename: Taro
authors.initials: T
authors.lastname: Shirakawa
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsubara
authors.forename: Akira
authors.initials: A
authors.lastname: Hata
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tamari
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Suzuki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C496556:GSTP1 protein, human