Variants in the 17q21 asthma susceptibility locus are associated with allergic rhinitis in the Japanese population

K. Tomita, M. Sakashita, T. Hirota, S. Tanaka, K. Masuyama, T. Yamada, S. Fujieda, A. Miyatake, N. Hizawa, Michiaki Kubo, Y. Nakamura, M. Tamari

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25 Citations (Scopus)

Abstract

Background Allergic rhinitis (AR) is a very common disorder peaking in the teenage years that is mediated by hypersensitivity responses to environmental allergens. Although it is well established that the ORMDL3 locus at chromosome 17q21 is associated with susceptibility to bronchial asthma, the genetic influences of the polymorphisms of the locus in allergic rhinitis are unclear. Objective To examine whether the polymorphisms in the 17q21 asthma susceptibility locus are associated with allergic rhinitis in the Japanese population. Methods We performed linkage disequilibrium (LD) mapping of the locus using the HapMap database and conducted an association study of the locus with a total of 15 tag SNPs in two independent populations. We further evaluated correlations of genotypes with changes in expression of genes at the region in lymphoblastoid cell lines in the Japanese population and assessed the expression levels of the genes in nasal epithelium and various human tissues. Results We found a significant association between a total of five polymorphisms in the 17q21 asthma susceptibility locus, rs9303277, rs7216389, rs7224129, rs3744246, and rs4794820, and AR (minimum Pcombined = 0.00074, rs4794820). The expression level of the ORMDL3 transcript was significantly correlated with the genotype of rs12150079, rs7216389, rs3744246, and rs4794820 with P < 0.01 (minimum P = 0.0058, rs7216389), and ORMDL3 mRNA was highly expressed in nasal epithelium. Conclusion Genetic variants in the 17q21 asthma susceptibility locus are significantly associated with AR in the Japanese population.

Original languageEnglish
Pages (from-to)92-100
Number of pages9
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume68
Issue number1
DOIs
Publication statusPublished - 01-01-2013

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Asthma
Nasal Mucosa
Population
Genotype
HapMap Project
Gene Expression
Chromosome Mapping
Linkage Disequilibrium
Allergens
Single Nucleotide Polymorphism
Hypersensitivity
Chromosomes
Allergic Rhinitis
Databases
Cell Line
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Tomita, K. ; Sakashita, M. ; Hirota, T. ; Tanaka, S. ; Masuyama, K. ; Yamada, T. ; Fujieda, S. ; Miyatake, A. ; Hizawa, N. ; Kubo, Michiaki ; Nakamura, Y. ; Tamari, M. / Variants in the 17q21 asthma susceptibility locus are associated with allergic rhinitis in the Japanese population. In: Allergy: European Journal of Allergy and Clinical Immunology. 2013 ; Vol. 68, No. 1. pp. 92-100.
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abstract = "Background Allergic rhinitis (AR) is a very common disorder peaking in the teenage years that is mediated by hypersensitivity responses to environmental allergens. Although it is well established that the ORMDL3 locus at chromosome 17q21 is associated with susceptibility to bronchial asthma, the genetic influences of the polymorphisms of the locus in allergic rhinitis are unclear. Objective To examine whether the polymorphisms in the 17q21 asthma susceptibility locus are associated with allergic rhinitis in the Japanese population. Methods We performed linkage disequilibrium (LD) mapping of the locus using the HapMap database and conducted an association study of the locus with a total of 15 tag SNPs in two independent populations. We further evaluated correlations of genotypes with changes in expression of genes at the region in lymphoblastoid cell lines in the Japanese population and assessed the expression levels of the genes in nasal epithelium and various human tissues. Results We found a significant association between a total of five polymorphisms in the 17q21 asthma susceptibility locus, rs9303277, rs7216389, rs7224129, rs3744246, and rs4794820, and AR (minimum Pcombined = 0.00074, rs4794820). The expression level of the ORMDL3 transcript was significantly correlated with the genotype of rs12150079, rs7216389, rs3744246, and rs4794820 with P < 0.01 (minimum P = 0.0058, rs7216389), and ORMDL3 mRNA was highly expressed in nasal epithelium. Conclusion Genetic variants in the 17q21 asthma susceptibility locus are significantly associated with AR in the Japanese population.",
author = "K. Tomita and M. Sakashita and T. Hirota and S. Tanaka and K. Masuyama and T. Yamada and S. Fujieda and A. Miyatake and N. Hizawa and Michiaki Kubo and Y. Nakamura and M. Tamari",
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Tomita, K, Sakashita, M, Hirota, T, Tanaka, S, Masuyama, K, Yamada, T, Fujieda, S, Miyatake, A, Hizawa, N, Kubo, M, Nakamura, Y & Tamari, M 2013, 'Variants in the 17q21 asthma susceptibility locus are associated with allergic rhinitis in the Japanese population', Allergy: European Journal of Allergy and Clinical Immunology, vol. 68, no. 1, pp. 92-100. https://doi.org/10.1111/all.12066

Variants in the 17q21 asthma susceptibility locus are associated with allergic rhinitis in the Japanese population. / Tomita, K.; Sakashita, M.; Hirota, T.; Tanaka, S.; Masuyama, K.; Yamada, T.; Fujieda, S.; Miyatake, A.; Hizawa, N.; Kubo, Michiaki; Nakamura, Y.; Tamari, M.

In: Allergy: European Journal of Allergy and Clinical Immunology, Vol. 68, No. 1, 01.01.2013, p. 92-100.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Variants in the 17q21 asthma susceptibility locus are associated with allergic rhinitis in the Japanese population

AU - Tomita, K.

AU - Sakashita, M.

AU - Hirota, T.

AU - Tanaka, S.

AU - Masuyama, K.

AU - Yamada, T.

AU - Fujieda, S.

AU - Miyatake, A.

AU - Hizawa, N.

AU - Kubo, Michiaki

AU - Nakamura, Y.

AU - Tamari, M.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Background Allergic rhinitis (AR) is a very common disorder peaking in the teenage years that is mediated by hypersensitivity responses to environmental allergens. Although it is well established that the ORMDL3 locus at chromosome 17q21 is associated with susceptibility to bronchial asthma, the genetic influences of the polymorphisms of the locus in allergic rhinitis are unclear. Objective To examine whether the polymorphisms in the 17q21 asthma susceptibility locus are associated with allergic rhinitis in the Japanese population. Methods We performed linkage disequilibrium (LD) mapping of the locus using the HapMap database and conducted an association study of the locus with a total of 15 tag SNPs in two independent populations. We further evaluated correlations of genotypes with changes in expression of genes at the region in lymphoblastoid cell lines in the Japanese population and assessed the expression levels of the genes in nasal epithelium and various human tissues. Results We found a significant association between a total of five polymorphisms in the 17q21 asthma susceptibility locus, rs9303277, rs7216389, rs7224129, rs3744246, and rs4794820, and AR (minimum Pcombined = 0.00074, rs4794820). The expression level of the ORMDL3 transcript was significantly correlated with the genotype of rs12150079, rs7216389, rs3744246, and rs4794820 with P < 0.01 (minimum P = 0.0058, rs7216389), and ORMDL3 mRNA was highly expressed in nasal epithelium. Conclusion Genetic variants in the 17q21 asthma susceptibility locus are significantly associated with AR in the Japanese population.

AB - Background Allergic rhinitis (AR) is a very common disorder peaking in the teenage years that is mediated by hypersensitivity responses to environmental allergens. Although it is well established that the ORMDL3 locus at chromosome 17q21 is associated with susceptibility to bronchial asthma, the genetic influences of the polymorphisms of the locus in allergic rhinitis are unclear. Objective To examine whether the polymorphisms in the 17q21 asthma susceptibility locus are associated with allergic rhinitis in the Japanese population. Methods We performed linkage disequilibrium (LD) mapping of the locus using the HapMap database and conducted an association study of the locus with a total of 15 tag SNPs in two independent populations. We further evaluated correlations of genotypes with changes in expression of genes at the region in lymphoblastoid cell lines in the Japanese population and assessed the expression levels of the genes in nasal epithelium and various human tissues. Results We found a significant association between a total of five polymorphisms in the 17q21 asthma susceptibility locus, rs9303277, rs7216389, rs7224129, rs3744246, and rs4794820, and AR (minimum Pcombined = 0.00074, rs4794820). The expression level of the ORMDL3 transcript was significantly correlated with the genotype of rs12150079, rs7216389, rs3744246, and rs4794820 with P < 0.01 (minimum P = 0.0058, rs7216389), and ORMDL3 mRNA was highly expressed in nasal epithelium. Conclusion Genetic variants in the 17q21 asthma susceptibility locus are significantly associated with AR in the Japanese population.

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