Identification of the susceptive genes for atopic diseases using positional candidate gene approaches.

• Project/Area Number: 11470504
• Research Category: Grant-in-Aid for Scientific Research (B).
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human genetics
• Research Institution: Institute of Basic Medical Sciences, University of Tsukuba
• Principal Investigator: HAMAGUCHI Hideo Institute of Basic Medical Sciences, Professor, 基礎医学系, 教授 (00091918)
• Co-Investigator(Kenkyū-buntansha): OTSUKA Fujio Institute of Clinical Medicine, Professor, 臨床医学系, 教授 (10092157) ; KOBAYASHI Kimiko Institute of Basic Medical Sciences, Assistant Professor, 基礎医学系, 講師 (90215319) ; ARINAMI Tadao Institute of Basic Medical Sciences, Associate Professor, 基礎医学系, 助教授 (10212648) ; SHIBASAKI Masanao Institute of Clinical Medicine, Associate Professor, 臨床医学系, 助教授 (30049233)
• Project Period (FY): 1999 – 2000
• Project Status: Completed (Fiscal Year 2000)
• Budget Amount: ¥14,600,000 (Direct Cost: ¥14,600,000); Fiscal Year 2000: ¥7,000,000 (Direct Cost: ¥7,000,000); Fiscal Year 1999: ¥7,600,000 (Direct Cost: ¥7,600,000)
• Keywords: atopic asthma / atopic dermatitis / linkage / maximum lod scores / ゲノムスキャン / 罹患同胞

Research Abstract

Childhood-onset asthma is frequently found in association with atopy. We conducted a genomewide linkage search in 47 Japanese families (197 members) with more than two mite-sensitive atopic asthmatics (65 affected sib-pairs) using 398 markers. Multipoint linkage analysis was carried out for atopic asthma as a quantitative trait using the MAPMAKER/SIB program. We observed significant evidence for linkage with maximum lod scores (MLS) of 4.8 on 5q31-q33. In addition, suggestive evidence on 4q35 with MLS=2.7 and on 13q11 with MLS=2.4 was obtained. The other possible linkage regions included 6p22-p21.3 (MLS=2.1), 12q21-q23 (MLS=1.9), and 13q14.1-q14.3 (MLS=2.0). Furthermore, we observed suggestive evidence for linkage with atopic dermatitis on 5q31-q33 and 12q21-q23. These data suggest that the chromosome region of 5q31-q33 and 12q21-q23 may be common susceptive region of atopic asthma and atopic dermatitis.

Research Products

• [Publications] Yokouchi Y et al.: "A Significant Evidence for Linkage of Mite-Sensitive Childhood Asthma to Chromosome 5q31-q33 nearthe Interleukin 12 B Locus by A Genome-wide Search in Japanese families."Genomics. 66. 152-160 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Noguchi E et al.: "Mutation screening of Interferon regulatory factor 1 gene(IRF-1) as a candidate gen for asthma."Clin Exp Allergy. 30. 1563-1567 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kimura K et al.: "Linkage and association of atopic asthma to markers on chromosome 13 in the Japanese population."Hum Mol Genet. 8. 1487-1490 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Noguchi E et al.: "No association between atopy/asthma and the ILe50Val polymorphism of IL-4 receptor."Am J Respir Crit Care Med. 160. 342-345 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ishizawa M et al.: "No association between atopic asthma and a coding variant of Fc ε R1 β in a Japanese population"J Hum Genet. 44. 308-311 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kimura K, Noguchi E, Shibasaki M, Arinami T, Hamaguchi H et al.: "Linkage and association of atopic asthma to markers on chromosome 13 in the Japanese population."Hum Mol Genet. 8. 1487-90 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Noguchi E, Shibasaki M, Arinami T, Hamaguchi H et al.: "No association between atopy/asthma and the ILe50Val polymorphism of IL-4 receptor."Am J Respir Crit Care Med. 160. 342-5 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Noguchi E, Shibasaki M, Arinami T, Hamaguchi H et al.: "Lack of association of atopy/asthma and the interleukin-4 receptor alpha gene in Japanese."Clin Exp Allergy. 29. 228-33 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ishizawa M, Shibasaki M, Yokouchi Y, Hamaguchi H et al.: "No association between atopic asthma and a coding variant of Fc ε R1 β in a Japanese population."J Hum Genet. 44. 308-11 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yokouchi Y, Nukaga Y, Shibasaki M, Noguchi E, Hamaguchi H et al.: "Significant evidence for linkage of mite-sensitive childhood asthma to chromosome 5q31-q33 near the interleukin 12 B locus by a genome-wide search in Japanese families."Genomics. 66. 152-60 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Noguchi E, Shibasaki M, Arinami T, Hamaguchi H et al.: "Mutation screening of interferon regulatory factor 1 gene (IRF-1) as a candidate gene for atopy/asthma."Clin Exp Allergy. 30. 1562-7 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yokouchi Y et al.: "A Significant Evidence for Linkage of Mite-Sensitive Childhood Asthma to Chromosome 5q31-q33 nearthe Interleukin 12 B Locus by A Genome-wide Search in Japanese families."Genomics. 66. 152-160 (2000)
• [Publications] Nakayama J et al.: "Significant evidence for linkage of febrile seizures to chromosome 5q14-q15."Hum Mol Genet. 9. 87-91 (2000)
• [Publications] Noguchi E et al.: "Mutation screening of Interferon regulatory factor 1 gene (IRF-1) as a candidate gene for asthma."Clin Exp Allergy. 30. 1563-1567 (2000)
• [Publications] Kazumi Kimura et al.: "Linkage and association of atopic asthma to markers on chromosome 13 in the Japanese population."Hum.Mol.Genet.. 8. 1487-1490 (1999)
• [Publications] Emiko Noguchi et al.: "No association between atopy/asthma and the Ile 50 Val polymorphism of IL4 receptor."Am.J.Resp.Crit.Care.Med.. 160. 342-345 (1999)
• [Publications] Yukako Yokouchi et al.: "A genome-wide search for linkage to childhood atopic asthma Susceptibility genes in the Japanese."Genomics. (in press).