Genetic Influences on Response to Leukotriene Receptor Antagonist(LTRA) in Asthma

• Project/Area Number: 19790703
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: HIROTA Tomomitsu The Institute of Physical and Chemical Research, 呼吸器疾患研究チーム, リサーチアソシエイト (50435674)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,300,000)
• Keywords: 気管支喘息 / ロイコトリエン受容体拮抗薬 / 遺伝子多型 / 個人差 / 多様性 / 個人差、多様性

Research Abstract

気管支喘息におけるロイコトリエン受容体拮抗薬(LTRA)の効果と遺伝子多型の関連について検討を行った。システニルロイコトリエン産生経路に関与する遺伝子についてスクリーニングを行った結果、LTC4S遺伝子においてLTRA投与後の呼吸機能の改善率と有意な相関を示すSNPを遺伝子上流の領域に見出した。その遺伝子多型がどのように呼吸機能の改善率に関与しているかを解明するために機能的解析を行った。

Research Products

• [Journal Article] Functional analysis of the Thymic Stromal Lymphopoietin Variants in Human Bronchial Epithelial Cells (2009)
  • Author(s): Harada M ,Hirota T, Jodo AI et al (2番目/16人)
  • Journal Title: Am J Respir Cell Mol Biol 40 Pages: 368-374
  • Peer Reviewed
• [Journal Article] Functional analysis of the polymorphisms of the TSLP gene in human bronchial epithelial cells (2009)
  • Author(s): Michishige Harada
  • Journal Title: American Journal of Respiratory Cell and Molecular Biology 40 Pages: 368-368
  • Peer Reviewed
• [Journal Article] Genetic polymorphism regulating ORM1-like 3 (Saccharomyces cerevisiae) expression is associated with childhood atopic asthma in a Japanese population (2008)
  • Author(s): Hirota T, Harada M, Sakashita M et al (1番目/13人)
  • Journal Title: J Allergy Clin Immunol 121(3) Pages: 769-70
  • Peer Reviewed
• [Journal Article] Association study of the C3 gene with adult and childhood asthma (2008)
  • Author(s): Inoue H, Mashimo Y , Hirota T et al (6番目/14人)
  • Journal Title: J Hum Genet 53(8) Pages: 728-38
  • NAID: 10021929109
  • Peer Reviewed
• [Journal Article] 特集 アレルギー疾患発症の胎内・胎外因子 アレルギー疾患発症における遺伝要因と感染の関与 (2008)
  • Author(s): 玉利真由美, 広田朝光, 原田通成, (2番目/3人)
  • Journal Title: アレルギー・免疫 15(2) Pages: 134-140
• [Journal Article] 特集:アレルギー疾患の遺伝 アレルギー性鼻炎 (2008)
  • Author(s): 坂下雅文, 広田朝光, 原田通成ら(2番目/4人)
  • Journal Title: アレルギー・免疫 15(7) Pages: 912-920
• [Journal Article] Genetic polymorphism regulating ORM1-like 3 (Saccharomyces cerevisiae) expression is associated with childhood atopic asthma in a Japanese population (2008)
  • Author(s): Tomomitsu Hirota
  • Journal Title: Journal of Allergy and Clinical Immunology 121 Pages: 769-769
  • Peer Reviewed
• [Journal Article] Association of serum IL-33 level and the IL-33 genetic variant with Japanese cedar pollinosis (2008)
  • Author(s): Masafumi Sakashita
  • Journal Title: Clinical & Experimental Allergy 38 Pages: 1875-1875
  • Peer Reviewed
• [Journal Article] Filaggrin null mutations are associated with atopic dermatitis and elevated levels of IgE in the Japanese population : a family and case-control study (2008)
  • Author(s): Hisako Enomoto
  • Journal Title: Journal of Human Genetics 53 Pages: 615-615
  • Peer Reviewed
• [Journal Article] Association study of the C3 gene with adult and childhood asthma (2008)
  • Author(s): Hiroki Inoue
  • Journal Title: Journal of Human Genetics 53 Pages: 728-728
  • Peer Reviewed
• [Journal Article] Transforming growth factor-beta(2) polymorphisms are associated with childhood atopic asthma (2007)
  • Author(s): Hatsushika K, Hirota T, Harada M et al (2番目/15人)
  • Journal Title: Clin Exp Allergy 37(8) Pages: 1165-1174
  • Peer Reviewed
• [Journal Article] Functional polymorphism in the suppressor of cytokine signaling 1 gene associated with adult asthma (2007)
  • Author(s): Harada M, Nakashima K, Hirota T et al (3番目/20人)
  • Journal Title: Am J Respir Cell Mol Biol 36(4) Pages: 491-6
  • Peer Reviewed
• [Journal Article] The GSTP1 gene is a susceptibility gene for childhood asthma and the GSTM1 gene is a modifier of the GSTP1 gene (2007)
  • Author(s): Kamada F, Mashimo Y, Hirota T et al (5番目/24人)
  • Journal Title: Int Arch Allergy Immunol 144(4) Pages: 275-286
  • Peer Reviewed
• [Journal Article] 喘息と遺伝学 重症喘息について (2007)
  • Author(s): 広田朝光, 原田通成,玉利真由美 (1番目/3人)
  • Journal Title: International Review of Asthma 9(4) Pages: 46-54
• [Journal Article] Transforming growth factor-β2 polymorphisms are associated with childhood atopic asthma (2007)
  • Author(s): Kyosuke Hatsushika
  • Journal Title: Clinical & Experimental Allergy 37 Pages: 1165-1174
  • Peer Reviewed
• [Journal Article] The GSTP1 Gene Is a Susceptibility Gene for Childhood Asthma and the GSTM1 Gene Is a Modifier of the GSTP1 Gene (2007)
  • Author(s): Fumiaki Kamada
  • Journal Title: International Archives of Allergy and Immunology 144 Pages: 275-286
  • Peer Reviewed
• [Journal Article] Functional Polymorphism in the Suppressor of Cytokine Signaling 1 Gene Associated with Adult Asthma (2007)
  • Author(s): Michishige Harada
  • Journal Title: American Journal of Respiratory Cell and Molecular Biology 36 Pages: 491-496
  • Peer Reviewed
• [Journal Article] 重症喘息について (2007)
  • Author(s): 広田朝光
  • Journal Title: International Review of Asthma 9 Pages: 46-54
• [Journal Article] 解説・基礎 日本人における気管支喘息関連遺伝子
  • Author(s): 広田朝光, 原田通成, 玉利真由美ら(1番目/5人)
  • Journal Title: 呼吸 in press
• [Journal Article] Genetic polymorphism regulating ORM1-like 3(Saccharomyces cerevisiae)expression is associated with childhood atopic asthma in a Japanese population.
  • Author(s): Tomomitsu Hirota
  • Journal Title: Journal of Allergy and Clinical Immunology In press
  • Peer Reviewed
• [Presentation] Genetic association studies of IL-13 gene in adult asthma and effects of IL-13 on the synthesis of chemokines by bronchial epithelial cells Keystone Symposia (2009)
  • Author(s): Tomomitsu Hirota
  • Organizer: Allergy and Asthma
  • Place of Presentation: Keystone, Colorado, USA
  • Year and Date: 2009-01-22
• [Presentation] Genetic association studies of IL-13 gene in adult asthma and effects of IL-13 on the synthesis of chemokines by bronchial epithelial cells (2009)
  • Author(s): Tomomitsu Hirota
  • Organizer: Keystone Symposia, Allergy and Asthma
  • Place of Presentation: Keystone, Colorado, USA
  • Year and Date: 2009-01-22
• [Presentation] 遺伝子多型の解析方法について (2008)
  • Author(s): 広田朝光
  • Organizer: 第58回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-28
• [Presentation] ORMDL3の発現を調節する遺伝子多型と日本人小児気管支喘息の相関解析 (2008)
  • Author(s): 広田朝光
  • Organizer: 第53回日本人類遺伝学会
  • Place of Presentation: 横浜
  • Year and Date: 2008-09-30
• [Presentation] ORMDL3の発現を調節する遺伝子多型と日本人小児気管支喘息の相関解析 (2008)
  • Author(s): 広田朝光
  • Organizer: 第20回日本アレルギー学会春季臨床大会
  • Place of Presentation: 横浜
  • Year and Date: 2008-06-14
• [Presentation] Association between genetic variation in Toll-like receptor 1 (TLR1) gene and adult bronchial asthma (2007)
  • Author(s): Tomomitsu Hirota
  • Organizer: The American Society of Human Genetics: 57th Annual Meeting
  • Place of Presentation: San Diego, California, USA
  • Year and Date: 2007-10-25
• [Presentation] Association between genetic variation in Toll-like receptor 1(TLR1) gene and adult bronchial asthma (2007)
  • Author(s): Tomomitsu Hirota
  • Organizer: The American Society of Human Genetics
  • Place of Presentation: San Diego, USA
  • Year and Date: 2007-10-25