An association study of asthma and related phenotypes with polymorphisms in negative regulator molecules of the TLR signaling pathway

Kazuko Nakashima, Tomomitsu Hirota, Kazuhiko Obara, Makiko Shimizu, Aya Jodo, Makoto Kameda, Satoru Doi, Kimie Fujita, Taro Shirakawa, Tadao Enomoto, Fumio Kishi, Shigemi Yoshihara, Kenji Matsumoto, Hirohisa Saito, Yoichi Suzuki, Yusuke Nakamura, Mayumi Tamari

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25 Citations (Scopus)

Abstract

Although associations between endotoxin exposure or respiratory infection and asthma have been recognized, the genetic effects in these conditions are unclear. Toll-like receptors (TLRs) play an essential role in innate host defense and in the control of adaptive immune responses. IL-1R-associated kinase-M (IRAK-M) and single immunoglobulin IL-1R-related molecule (SIGIRR) negatively regulate TLR-signaling pathways. To investigate whether polymorphisms in these genes were associated with asthma or asthma-related phenotypes, we screened these genes for polymorphisms by direct sequencing of 24 asthmatics and identified 19 variants in IRAK-M and 12 variants in SIGIRR. We next conducted linkage disequilibrium mapping of the genes, and examined the association of polymorphisms and haplotypes using 391 child patients with asthma, 462 adult patients with asthma, and 639 controls. None of the alleles or haplotypes of IRAK-M and SIGIRR were associated with asthma susceptibility or asthma-related phenotype. Our results indicate that polymorphisms in IRAK-M and SIGIRR are not likely to be associated with the development of asthma in the Japanese population.

Original languageEnglish
Pages (from-to)284-291
Number of pages8
JournalJournal of Human Genetics
Volume51
Issue number4
DOIs
Publication statusPublished - 2006 Apr 1

Keywords

  • Association study
  • Asthma
  • Haplotype
  • IRAK-M
  • Japanese population
  • SIGIRR
  • Single nucleotide polymorphism (SNP)
  • Toll-like receptors (TLRs)

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    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. (2006). An association study of asthma and related phenotypes with polymorphisms in negative regulator molecules of the TLR signaling pathway. Journal of Human Genetics, 51(4), 284-291. https://doi.org/10.1007/s10038-005-0358-1