Association between genetic variation in the gene for death-associated protein-3 (DAP3) and adult asthma

Tomomitsu Hirota, Kazuhiko Obara, Akira Matsuda, Mitsuteru Akahoshi, Kazuko Nakashima, Koichi Hasegawa, Naomi Takahashi, Makiko Shimizu, Hiroshi Sekiguchi, Miki Kokubo, Satoru Doi, Hiroshi Fujiwara, Akihiko Miyatake, Kimie Fujita, Tadao Enomoto, Fumio Kishi, Yoichi Suzuki, Hirohisa Saito, Yusuke Nakamura, Taro ShirakawaMayumi Tamari

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Lung epithelium plays a central role in modulation of the lung inflammatory response, and lung repair and airway epithelial cells are targets in asthma and viral infection. Activated T lymphocytes release cytokines such as interferon-gamma (IFN-γ) that induce apoptosis, or programmed cell death, of damaged epithelial cells. Death-associated protein-3 (DAP3) is involved in mediating IFN-γ-induced cell death. To assess the possible involvement of genetic variants of DAP3 with asthma, we searched for single-nucleotide polymorphisms (SNPs) in the gene and conducted a case-control study with 1,341 subjects. We found a strong association between bronchial asthma (BA) in adults (P = 0.0051, odds ratio = 1.87, 95% CI= 1.20-2.92), whereas no association was found with childhood asthma. The tendency was more prominent in patients with higher serum total immunoglobulin E (IgE) (>250IU/ml) (P = 0.00061, odds ratio = 2.40, 95% CI= 1.44-4.00). DAP3 was expressed in normal bronchial epithelial cells, and the expression was induced by IFN-γ. These results indicated that specific variants of the DAP3 gene might be associated with the mechanisms responsible for adult BA and contribute to airway inflammation and remodeling.

Original languageEnglish
Pages (from-to)370-375
Number of pages6
JournalJournal of Human Genetics
Volume49
Issue number7
DOIs
Publication statusPublished - 2004 Jan 1

Keywords

  • Association study
  • Bronchial asthma
  • DAP3
  • Immunoglobulin E
  • Single-nucleotide polymorphism

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Hirota, T., Obara, K., Matsuda, A., Akahoshi, M., Nakashima, K., Hasegawa, K., Takahashi, N., Shimizu, M., Sekiguchi, H., Kokubo, M., Doi, S., Fujiwara, H., Miyatake, A., Fujita, K., Enomoto, T., Kishi, F., Suzuki, Y., Saito, H., Nakamura, Y., ... Tamari, M. (2004). Association between genetic variation in the gene for death-associated protein-3 (DAP3) and adult asthma. Journal of Human Genetics, 49(7), 370-375. https://doi.org/10.1007/s10038-004-0161-4