Influence between genetic variant of oxidative stress relating gene CYP1A1 and allergic rhinitis

• Project/Area Number: 22791583
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Otorhinolaryngology
• Research Institution: University of Fukui
• Principal Investigator: SAKASHITA Masafumi 福井大学, 医学部・附属病院, 助教 (40555455)
• Research Collaborator: FUJIEDA Shigeharu 福井大学, 医学部, 教授 (30238539)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 鼻科学 / 鼻アレルギー / アレルギー性鼻炎 / 遺伝子多型 / CYP1A1 / SNPs

Research Abstract

Oxidative stress is one of a key components of inflammation for upper airway diseases. Diesel exhaust particles(DEP) and asian sand dust increase oxidative stress and influence upper airway disorder including allergic rhinisis. Cytochrom 1A1(CYP1A1) is one of the Cytochrome P450 enzymes, catalyze the biotransformation of a wide variety of xenobiotic compaounds such as DEP and asian sand dust. We screened single-nucleotide polymorphisms(SNPs) at the CYP1A1 locus and performed an association study in the Japanese population.(619 patients with allergic rhinitis, 311 controls) Functional analysis of the SNP using transient transfection reporter gene assay was conducted. We identified 9SNPs at this locus and found this region consisted of one linkage disequilibrium block represented by three SNPs(tag SNPs). The association between the intron 1 polymorphism in the CYP1A1 gene and adult allergic rhinitis was significant.(p=0. 002, OR=1. 51, 95% C. I.=1. 1-1. 7) Risk allele containing construct showed significantly lower induction of CYP1A1 promoter activity in reporter gene assay.(p<0. 01) Our results support a role for CYP1A1 in the pathogenesis of allergic rhinitis in the Japanese population.

Research Products

• [Journal Article] V.アレルギー性鼻炎のゲノム解析の現況 (2011)
  • Author(s): 坂下雅文、藤枝重治
  • Journal Title: アレルギー・免疫 Volume: Vol.18, No.9 Pages: 38-46
• [Journal Article] 花粉症の遺伝～子供に花粉症は遺伝するのか?～ (2011)
  • Author(s): 坂下雅文、藤枝重治
  • Journal Title: チャイルドヘルス Volume: Vol.15, No.2 Pages: 8-12
• [Journal Article] 免疫療法の作用メカニズム (2011)
  • Author(s): 藤枝重治, 坂下雅文, 窪誠太, 大澤陽子
  • Journal Title: 喘息 Volume: 24(1) Pages: 2-7
• [Journal Article] Variants of C-C motif chemokine 22 (CCL22) are associated with susceptibility to atopic dermatitis : case-control studies (2011)
  • Author(s): Hirota, T., et.al.
  • Journal Title: PLoS One Volume: 6(11) Issue: 11 Pages: e26987-e26987
  • DOI: 10.1371/journal.pone.0026987
  • Peer Reviewed
• [Journal Article] B type CpG-DNA suppresses poly (I:C)-induced BLyS expression and production in human tonsillar fibroblasts (2011)
  • Author(s): Yamada T, et al
  • Journal Title: Clin Immunol Volume: 141 Issue: 3 Pages: 365-71
  • DOI: 10.1016/j.clim.2011.09.012
  • Peer Reviewed
• [Journal Article] Genome-wide association study identifies HLA-DP as a susceptibility gene for pediatric asthma in Asian populations (2011)
  • Author(s): Noguchi E, Sakamoto H, Hirota T, Ochiai K, Imoto Y, Sakashita M, Kurosaka F, Akasawa A, Yoshihara S, Kanno N, Yamada Y, Shimojo N, Kohno Y, Suzuki Y, Kang MJ, Kwon JW, Hong SJ, Inoue K, Goto Y, Yamashita F, Asada T, Hirose H, Saito I, Fujieda S, Hizawa N, Sakamoto T, Masuko H, Nakamura Y, Nomura I, Tamari M, Arinami T, Yoshida T, Saito H, Matsumoto K
  • Journal Title: PLoS Genet Volume: 7(7) Issue: 7 Pages: 1002170-1002170
  • DOI: 10.1371/journal.pgen.1002170
  • Peer Reviewed
• [Presentation] Epidemiological analysis of eosinophilic chronicrhinosinusitis in Japan (2011)
  • Author(s): 坂下雅文
  • Organizer: 11th Japan-Taiwan Conference on Otolaryngo logy-Head and Neck Surgery
  • Place of Presentation: 兵庫
  • Year and Date: 2011-12-08
• [Presentation] 好酸球性副鼻腔炎の診断および評価基準作成の試み、全国12施設(3015例)の副鼻腔手術から解析した好酸球性副鼻腔炎の術前診断 (2011)
  • Author(s): 坂下雅文
  • Organizer: 第40回鼻科学臨床問題懇話会
  • Place of Presentation: 岡山(招待講演)
  • Year and Date: 2011-12-01
• [Presentation] Association between genetic variant of interleukin (IL)-33 and allergic rhinitis in the Japanese population (2011)
  • Author(s): 坂下雅文
  • Organizer: XIVIRS-XXXISIAN
  • Place of Presentation: 東京
  • Year and Date: 2011-09-20
• [Presentation] The impact of Asian sand Dust on allergic rhinitis (2011)
  • Author(s): 坂下雅文
  • Organizer: 第42回日本職業・環境アレルギー学会総会・学術大会
  • Place of Presentation: 愛知(招待講演)
  • Year and Date: 2011-06-03
• [Presentation] Association between genetic variant of interleukin(IL)-33 and allergic rhinitis in the Japanese population (2011)
  • Author(s): Masafumi Sakashita, ほか6名
  • Organizer: XIVIRS-XXXISIAN
  • Place of Presentation: 東京
• [Presentation] The impact of Asian sand Dust on allergic rhinitis (2011)
  • Author(s): Masafumi Sakashita, ほか8名
  • Organizer: 第42回日本職業・環境アレルギー学会総会・学術大会
  • Place of Presentation: 愛知
• [Presentation] スギ花粉症患者の症状への黄砂の影響 (2011)
  • Author(s): 坂下雅文, ほか6名
  • Organizer: 第23回日本アレルギー学会春季臨床大会一般講演(ポスター)
  • Place of Presentation: 千葉
• [Presentation] スギ特異的舌下免疫療法の治療効果に相関するマーカー分子の検討(2) (2011)
  • Author(s): 坂下雅文, ほか6名
  • Organizer: 第29回日本耳鼻咽喉科免疫アレルギー学会
  • Place of Presentation: 大分
• [Presentation] スギ花粉症患者の症状への黄砂の影響 (2011)
  • Author(s): 坂下雅文
  • Organizer: 第23回日本アレルギー学会春季臨床大会
  • Place of Presentation: 千葉
• [Presentation] 小児気管支喘息関連領域17q21のSNPsとアレルギー性鼻炎との関連解析 (2010)
  • Author(s): 坂下雅文
  • Organizer: 第60回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京
  • Year and Date: 2010-11-25
• [Presentation] リアルタイムモニター(KH-3000)を用いた花粉測定 (2010)
  • Author(s): 坂下雅文
  • Organizer: 第22回日本アレルギー学会春季学術大会
  • Place of Presentation: 京都
  • Year and Date: 2010-05-08