An association study of asthma and related phenotypes with polymorphisms in negative regulator molecules of the TLR signaling pathway.
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.
Nakashima
Kazuko
K
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.
Hirota
Tomomitsu
T
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.
Obara
Kazuhiko
K
Laboratory for Genetics of Allergic Diseases, RIKEN SNP Research Center, 1-7-22 Suehiro, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
Shimizu
Makiko
M
Laboratory for Genetics of Allergic Diseases, RIKEN SNP Research Center, 1-7-22 Suehiro, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
Jodo
Aya
A
Laboratory for Genetics of Allergic Diseases, RIKEN SNP Research Center, 1-7-22 Suehiro, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
Kameda
Makoto
M
Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, Japan.
Doi
Satoru
S
Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, Japan.
Fujita
Kimie
K
School of Human Nursing, The University of Shiga Prefecture, Shiga, Japan.
Shirakawa
Taro
T
Department of Health Promotion and Human Behavior, Kyoto University School of Public Health, Kyoto, Japan.
Enomoto
Tadao
T
Department of Otolaryngology, Japanese Red Cross Society, Wakayama Medical Center, Wakayama, Japan.
Kishi
Fumio
F
Department of Microbiology and Immunology, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, Japan.
Yoshihara
Shigemi
S
Department of Pediatrics, Dokkyo University School of Medicine, Dokkyo, Japan.
Matsumoto
Kenji
K
Department of Allergy and Immunology, National Research Institute for Child Health & Development, Tokyo, Japan.
Saito
Hirohisa
H
Department of Allergy and Immunology, National Research Institute for Child Health & Development, Tokyo, Japan.
Suzuki
Yoichi
Y
Department of Public Health, Graduate School of Medicine, Chiba University, Chiba, Japan.
Nakamura
Yusuke
Y
Laboratory of Molecular Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Tamari
Mayumi
M
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.
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*
D051193:Toll-Like Receptors