Variants in the 17q21 asthma susceptibility locus are associated with allergic rhinitis in the Japanese population
Variants in the 17q21 asthma susceptibility locus are associated with allergic rhinitis in the Japanese population
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DOI：
10.1111/all.12066
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发表时间：
2013-01-01
期刊：
影响因子：
12.4
通讯作者：
Tamari, M.
中科院分区：
文献类型：
--
作者：
Tomita, K.;Sakashita, M.;Tamari, M.
变应性鼻炎（AR）是一种非常常见的疾病，在青少年时期达到高峰，是由对环境过敏原的超敏反应介导的。尽管染色体17q21上的ORMDL3基因座与支气管哮喘易感性相关，目的探讨日本人群17q21哮喘易感基因多态性与变应性鼻炎的相关性。使用HapMap数据库对该基因座进行作图，并在两个独立群体中进行该基因座与总共15个标签SNP的关联研究。我们进一步评估了基因型与日本人群中淋巴母细胞样细胞系中该区域基因表达变化的相关性，并评估了鼻上皮和各种人体组织中基因的表达水平。rs3744246和rs4794820以及AR（最小P组合= 0.00074，rs4794820）。ORMDL3转录本的表达水平与rs12150079、rs7216389、rs3744246和rs4794820基因型显著相关（P < 0.01（最小P = 0.0058，rs7216389），结论日本人群中17q21哮喘易感基因的遗传变异与AR显著相关。
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.