The GSTP1 gene is a susceptibility gene for childhood asthma and the GSTM1 gene is a modifier of the GSTP1 gene

Fumiaki Kamada, Yoichi Mashimo, Hiroki Inoue, Chenchen Shao, Tomomitsu Hirota, Satoru Doi, Makoto Kameda, Hiroshi Fujiwara, Kimie Fujita, Tadao Enomoto, Sei Sasaki, Hiroko Endo, Reiko Takayanagi, Chifuyu Nakazawa, Toshio Morikawa, Miki Morikawa, Shigeaki Miyabayashi, Yasushi Chiba, Gen Tamura, Taro ShirakawaYoichi Matsubara, Akira Hata, Mayumi Tamari, Yoichi Suzuki

Research output: Contribution to journalArticle

35 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)275-286
Number of pages12
JournalInternational archives of allergy and immunology
Volume144
Issue number4
DOIs
Publication statusPublished - 2007 Nov 1

Keywords

  • Association study
  • Asthma
  • GSTM1
  • GSTP1
  • Gene-gene interaction
  • Haplotype
  • Japanese population
  • SNP

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Kamada, F., Mashimo, Y., Inoue, H., Shao, C., Hirota, T., Doi, S., Kameda, M., Fujiwara, H., Fujita, K., Enomoto, T., Sasaki, S., Endo, H., Takayanagi, R., Nakazawa, C., Morikawa, T., Morikawa, M., Miyabayashi, S., Chiba, Y., Tamura, G., ... Suzuki, Y. (2007). The GSTP1 gene is a susceptibility gene for childhood asthma and the GSTM1 gene is a modifier of the GSTP1 gene. International archives of allergy and immunology, 144(4), 275-286. https://doi.org/10.1159/000106316