Association between genetic variation in the gene for death-associated protein-3 (DAP3) and adult asthma.
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.
Hirota
Tomomitsu
T
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.
Obara
Kazuhiko
K
Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa 230-0045, Japan.
Matsuda
Akira
A
Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa 230-0045, Japan.
Akahoshi
Mitsuteru
M
Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa 230-0045, Japan.
Nakashima
Kazuko
K
Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Public Health, Kyoto, Japan.
Hasegawa
Koichi
K
Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Public Health, Kyoto, Japan.
Takahashi
Naomi
N
Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa 230-0045, Japan.
Shimizu
Makiko
M
Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa 230-0045, Japan.
Sekiguchi
Hiroshi
H
Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa 230-0045, Japan.
Kokubo
Miki
M
Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa 230-0045, Japan.
Doi
Satoru
S
Osaka Prefectural Habikino Hospital, Osaka, Japan.
Fujiwara
Hiroshi
H
Osaka Prefectural Habikino Hospital, Osaka, Japan.
Miyatake
Akihiko
A
Miyatake Asthma Clinic, Osaka, Japan.
Fujita
Kimie
K
College of Nursing, University of Shiga, Shiga, Japan.
Enomoto
Tadao
T
Wakayama Medical Center, Japanese Red Cross Society, Wakayama, Japan.
Kishi
Fumio
F
Department of Microbiology and Immunology, Kagoshima University Dental School, Kagoshima, Japan.
Suzuki
Yoichi
Y
Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
Saito
Hirohisa
H
Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
Nakamura
Yusuke
Y
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Shirakawa
Taro
T
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.
Tamari
Mayumi
M
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.
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
D051017:Apoptosis Regulatory Proteins; C097041:DAP3 protein, human; D011506:Proteins; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D007073:Immunoglobulin E; D007371:Interferon-gamma