Department of Pediatrics, University Medical Centre Maribor, Maribor, Slovenia.
Pharmacogenomics J. 2013 Dec;13(6):523-9. doi: 10.1038/tpj.2012.36. Epub 2012 Sep 18.
Recent genome-wide association studies linked childhood asthma with single-nucleotide polymorphisms (SNPs) in ORM1-like protein 3 (ORMDL3) gene region on chromosome 17q21. We analyzed the effect of functional SNP rs2872507 in ORMDL3 gene region on the response to antiasthmatic treatment with inhaled corticosteroids (ICSs) and ORMDL3 gene expression. Forced expiratory volume in 1 s increased significantly by 13.3% of predicted value after therapy in atopic asthmatics with AA genotype, compared with 7.0% in heterozygotes and 4.9% increase in GG homozygotes (P=0.0176). Median relative expression of ORMDL3 gene in asthmatics with AA, AG and GG genotypes was 0.75, 1.05 and 1.21, respectively (P<0.0001). Treatment with ICSs was significantly associated with the increase of median relative expression of ORMDL3 gene, from 0.88 to 1.21 (P=0.0032) in atopic asthmatics. Our results suggest that rs2872507 is associated with ORMDL3 gene expression and with ICS treatment response in children with atopic asthma.
最近的全基因组关联研究将儿童哮喘与 17q21 染色体上的 ORM1 样蛋白 3（ORMDL3）基因区域的单核苷酸多态性（SNPs）联系起来。我们分析了 ORMDL3 基因区域中功能性 SNP rs2872507 对吸入性皮质类固醇（ICSs）抗哮喘治疗反应和 ORMDL3 基因表达的影响。在特应性哮喘患者中，与杂合子相比，AA 基因型患者的 1 秒用力呼气量（FEV1）增加了 13.3%，而杂合子增加了 7.0%，GG 纯合子增加了 4.9%（P=0.0176）。AA、AG 和 GG 基因型哮喘患者的 ORMDL3 基因中位相对表达分别为 0.75、1.05 和 1.21（P<0.0001）。ICS 治疗与 ORMDL3 基因中位相对表达的增加显著相关，特应性哮喘患者的中位相对表达从 0.88 增加到 1.21（P=0.0032）。我们的研究结果表明，rs2872507 与 ORMDL3 基因表达和特应性哮喘儿童 ICS 治疗反应有关。
