title: An association study of asthma and related phenotypes with polymorphisms in negative regulator molecules of the TLR signaling pathway.
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.
authors.affiliation: Laboratory for Genetics of Allergic Diseases, RIKEN SNP Research Center, 1-7-22 Suehiro, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.|Department of Health Promotion and Human Behavior, Kyoto University School of Public Health, Kyoto, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Nakashima
authors.affiliation: Laboratory for Genetics of Allergic Diseases, RIKEN SNP Research Center, 1-7-22 Suehiro, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.|Department of Microbiology and Immunology, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, Japan.
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Hirota
authors.affiliation: Laboratory for Genetics of Allergic Diseases, RIKEN SNP Research Center, 1-7-22 Suehiro, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Obara
authors.affiliation: Laboratory for Genetics of Allergic Diseases, RIKEN SNP Research Center, 1-7-22 Suehiro, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Laboratory for Genetics of Allergic Diseases, RIKEN SNP Research Center, 1-7-22 Suehiro, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Jodo
authors.affiliation: Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kameda
authors.affiliation: Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Doi
authors.affiliation: School of Human Nursing, The University of Shiga Prefecture, Shiga, Japan.
authors.forename: Kimie
authors.initials: K
authors.lastname: Fujita
authors.affiliation: Department of Health Promotion and Human Behavior, Kyoto University School of Public Health, Kyoto, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Shirakawa
authors.affiliation: Department of Otolaryngology, Japanese Red Cross Society, Wakayama Medical Center, Wakayama, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Enomoto
authors.affiliation: Department of Microbiology and Immunology, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Kishi
authors.affiliation: Department of Pediatrics, Dokkyo University School of Medicine, Dokkyo, Japan.
authors.forename: Shigemi
authors.initials: S
authors.lastname: Yoshihara
authors.affiliation: Department of Allergy and Immunology, National Research Institute for Child Health & Development, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Allergy and Immunology, National Research Institute for Child Health & Development, Tokyo, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Saito
authors.affiliation: Department of Public Health, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Laboratory of Molecular Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Laboratory for Genetics of Allergic Diseases, RIKEN SNP Research Center, 1-7-22 Suehiro, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan. tamari@src.riken.jp.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tamari
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002877:Chromosomes, Human; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D051193:Toll-Like Receptors