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.
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Acknowledgements
We thank all patients and their families, the volunteers who served as controls, and all staff members at the hospitals involved in this study. We are grateful to the members of The Rotary Club of Osaka-Midosuji District 2660 Rotary International in Japan for supporting our study. We also thank Hiroshi Sekiguchi and Miki Kokubo for excellent technical assistance and Chinatsu Fukushima for providing patient data. This work was supported by Grants-in-Aid from The Ministry of Health, Labor and Welfare, Japan Science and Technology Corporation and the Japanese Millennium Project.
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Nakashima, K., Hirota, T., Obara, K. et al. An association study of asthma and related phenotypes with polymorphisms in negative regulator molecules of the TLR signaling pathway. J Hum Genet 51, 284–291 (2006). https://doi.org/10.1007/s10038-005-0358-1
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DOI: https://doi.org/10.1007/s10038-005-0358-1
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