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Keywords:

  • 17q21;
  • allergic rhinitis;
  • association;
  • Japanese;
  • single-nucleotide polymorphism

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 < 0.01 (minimum = 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.