Multivariate analysis of asthma susceptibility genes

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 16590260
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human genetics
• Research Institution: Chiba University
• Principal Investigator: SUZUKI Yoichi Chiba University, Graduate School of Medicine, Associate professor, 大学院・医学研究院, 助教授 (80216457)
• Co-Investigator(Kenkyū-buntansha): KURE Shigeo Tohoku University, Medical Genetics, Associate Professor, 大学院・医学研究科, 助教授 (10205221) ; MATSUBARA Yoichi Tohoku University, Medical Genetics, Professor, 大学院・医学研究科, 教授 (00209602)
• Project Period (FY): 2004 – 2005
• Keywords: bronchial asthma / single nucleotide polymorphism / multivariate analysis / haplotype / interleukin / complements / leukotrienes

Research Abstract

The changes in sensitivity and specificity of a test under different cut-off points can be overviewed by the receiver operating characteristic (ROC) curve. The area under ROC curve (AUC) indicates the discriminative ability of a clinical test. Susceptibility to a complex genetic disease such as bronchial asthma is not determined by a single gene but by a set of genes. We evaluated the usefulness of genetic tests with multiple candidate genes for asthma in the Japanese population with AUC. Using 629 controls, 484 adult asthmatics, 384 child asthmatics, we screened 320 SNPs in 80 asthma candidate genes. Ten (C3,TAP2,TLR3,IL12B,IL4RA,CYSLT2,ADRB2,IKAP,IFNB,IFNGR1) and 9 (MD1,MYD88,SERPNA1,STAT4,TLR2,TLR5,CYSLT2,C3,C5AR) genes showed significant association (P<0.05) with adult and childhood asthma, respectively. Screening of gene-gene interactions found 2 possible interactions for childhood asthma and one for adult asthma risk. These genes and gene-gene interactions were used as variables in logistic regression analyses. Prediction of the disease by multiple genes with logistic regression formula was clearly better than that by single gene. The AUC values for adult and childhood asthma were 0.721 and 0.887, respectively. The Nagelkerke's R square values for adult and child were 0.231 and 0.549, respectively. Only one gene (C3) was common to childhood and adult asthma. These results suggested difference in genetic backgrounds between adult and childhood asthma.

Research Products

• [Journal Article] An association study of asthma and related phenotypes with polymorphisms in negative regulator molecules of the TLR signaling pathway (2006)
  • Author(s): Nakashima K et al.
  • Journal Title: J Hum Genet (in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Association of the RIP2 gene with childhood atopic asthma (2006)
  • Author(s): Nakashima K et al.
  • Journal Title: Allergology International (in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Association between ADAM33 polymorphisms and adult asthma in the Japanese population (2006)
  • Author(s): Tamari M et al.
  • Journal Title: Clin Exp Allergy (in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] An association study of asthma and related phenotypes with polymorphisms in negative regulator molecules of the TLR signaling pathway (2006)
  • Author(s): Nakashima, K., Hirota, T., Obara, K., Shimizu, M., Jodo, A., Kameda, M., Doi, S., Fujita, K., Shirakawa, T., Enomoto, T., Kishi, F., Yoshihara, S., Matsumoto, K., Saito, H., Suzuki, Y., Nakamura, Y., Tamari, M.
  • Journal Title: J Hum Genet (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Association of the RIP2 gene with childhood atopic asthma (2006)
  • Author(s): Nakashima, K., Hirota, T., Suzuki, Y., Matsuda, A., Akahoshi, M., Shimizu, M., Hasegawa, K., Jodo, A., Doi, S., Fujita, K., Ebisawa, M., Yoshihara, S., Enomoto, T., Shirakawa, T., Obara, K., Kishi, F., Nakamura, Y., Tamari, M.
  • Journal Title: Allergology International (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Association between ADAM33 polymorphisms and adult asthma in the Japanese population (2006)
  • Author(s): Tamari, M., Hirota, T., Hasegawa, K., Obara, K., Matsuda, A., Akahoshi, M., Nakashima, K., Doi, S., Fujita, K., Suzuki, Y., Nakamura, Y., Shirakawa, T.
  • Journal Title: Clin Exp Allergy (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Functional haplotypes of IL-12B are associated with childhood atopic asthma (2005)
  • Author(s): Hitora T et al.
  • Journal Title: J allergy Clin Immunol 116 Pages: 789-795
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Functional haplotypes of IL-12B are associated with childhood atopic asthma (2005)
  • Author(s): Hirota, T., Suzuki, Y., Hasegawa, K., Obara, K., Matsuda, A., Akahoshi, M., Nakashima, K., Cheng, L., Takahashi, N., Shimizu, M., Doi, S., Fujita, K., Enomoto, T., Ebisawa, M., Yoshihara, S., Nakamura, Y., Kishi, R, Shirakawa, T., Tamari, M.
  • Journal Title: J Allergy Clin Immunol 116 Pages: 789-795
  • Description: 「研究成果報告書概要(欧文)」より