title: Association between genetic variation in the gene for death-associated protein-3 (DAP3) and adult asthma.
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-gamma) that induce apoptosis, or programmed cell death, of damaged epithelial cells. Death-associated protein-3 (DAP3) is involved in mediating IFN-gamma-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) (>250 IU/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-gamma. 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.
authors.affiliation: Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa 230-0045, Japan.|Department of Microbiology and Immunology, Kagoshima University Dental School, Kagoshima, Japan.
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Hirota
authors.affiliation: Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa 230-0045, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Obara
authors.affiliation: Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa 230-0045, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
authors.affiliation: Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa 230-0045, Japan.
authors.forename: Mitsuteru
authors.initials: M
authors.lastname: Akahoshi
authors.affiliation: Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Public Health, Kyoto, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Nakashima
authors.affiliation: Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Public Health, Kyoto, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa 230-0045, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa 230-0045, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa 230-0045, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sekiguchi
authors.affiliation: Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa 230-0045, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Kokubo
authors.affiliation: Osaka Prefectural Habikino Hospital, Osaka, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Doi
authors.affiliation: Osaka Prefectural Habikino Hospital, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujiwara
authors.affiliation: Miyatake Asthma Clinic, Osaka, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Miyatake
authors.affiliation: College of Nursing, University of Shiga, Shiga, Japan.
authors.forename: Kimie
authors.initials: K
authors.lastname: Fujita
authors.affiliation: Wakayama Medical Center, Japanese Red Cross Society, Wakayama, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Enomoto
authors.affiliation: Department of Microbiology and Immunology, Kagoshima University Dental School, Kagoshima, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Kishi
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Saito
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa 230-0045, Japan.|Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Public Health, Kyoto, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Shirakawa
authors.affiliation: Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa 230-0045, Japan. tamari@src.riken.go.jp.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tamari
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D016923:Cell Death; D002648:Child; D002675:Child, Preschool; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007223:Infant; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins; D013601:T-Lymphocytes / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D051017:Apoptosis Regulatory Proteins; C097041:DAP3 protein, human; D011506:Proteins; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D007073:Immunoglobulin E; D007371:Interferon-gamma