Variants in the 17q21 asthma susceptibility locus are associated with allergic rhinitis in the Japanese population. Issue 1 (12th November 2012)

• Record Type: Journal Article
• Authors: Tomita, K.; Sakashita, M.; Hirota, T.; Tanaka, S.; Masuyama, K.; Yamada, T.; Fujieda, S.; Miyatake, A.; Hizawa, N.; Kubo, M.; Nakamura, Y.; Tamari, M.
• Is Part Of: Allergy. Volume 68:Issue 1(2013:Jan.)
• Page Start: 92
• Page End: 100
• Publication Date: 2012-11-12
• Subjects: Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.12066
• Languages: English
• ISSNs: 0105-4538

Abstract

<abstract abstract-type="main" id="all12066-abs-0001"> <title>Abstract</title> <sec id="all12066-sec-0001" sec-type="section"> <title>Background</title> <p>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 <italic>ORMDL3</italic> 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.</p> </sec> <sec id="all12066-sec-0002" sec-type="section"> <title>Objective</title> <p>To examine whether the polymorphisms in the 17q21 asthma susceptibility locus are associated with allergic rhinitis in the Japanese population.</p> </sec> <sec id="all12066-sec-0003" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="all12066-sec-0004" sec-type="section"> <title>Results</title> <p>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 <italic>P</italic><sub>combined</sub> = 0.00074, rs4794820). The expression level of the <italic>ORMDL3</italic> transcript was significantly correlated with the genotype of rs12150079, rs7216389, rs3744246, and rs4794820 with <italic>P </italic><<italic> </italic>0.01 (minimum <italic>P </italic>=<italic> </italic>0.0058, rs7216389), and <italic>ORMDL3 </italic>mRNA was highly expressed in nasal epithelium.</p> </sec> <sec id="all12066-sec-0005" sec-type="section"> <title>Conclusion</title> <p>Genetic variants in the 17q21 asthma susceptibility locus are significantly associated with AR in the Japanese population.</p> </sec> </abstract>