Screening for genetic polymorphisms of histamine H1 and NK1 receptors which are involved in development of hyperreactivity of the nose

我们筛选了组胺H1和P物质（NK1）受体的遗传多态性，这些受体参与了鼻高反应性的发展。在本研究中，我们招募了48名符合以下标准之一的患者：（1）具有过敏原特异性IgE，但没有过度反应性鼻症状，（2）具有过敏原特异性IgE和过度反应性鼻症状，即鼻过敏，（3）过敏原特异性IgE阴性，但具有过度反应性鼻症状，即血管性鼻炎。患者数量分别为（1）23例、（2）20例和（3）5例。在获得知情同意后，从他们的血液中提取DNA，并对这些基因编码区的遗传多态性进行分析。采用聚合酶链反应（PCR）和单链构象多态性（SSCP）分析相结合的方法，在（1）组的1例患者中发现了H1受体基因第349位密码子的多态性（GAT*CAT，Asp349*His349）。她具有异质性的多态性。虽然它可能有助于患者的鼻低反应性，但由于其在人群中的频率较低，因此认为该多态性的意义仍然不大。在NK 1受体基因方面，分别在第1和第5外显子发现了两个沉默突变。前者位于密码子111（TTC*TTT，Phe111），后者位于密码子378（TCG*TCA，Ser378）。由于这些基因多态性不改变NK1受体的结构，因此它们在鼻高反应性的发病机制中没有意义。另一项筛选这些基因启动子区突变的研究将在以后进行

We screened for genetic polymorphisms of histamine H1 and substance P (NK1) receptors which are involved in development of hyperreactivity of the nose. For this study we enrolled 48 patients who met one of the following criteria : (1) one who has IgE specific for an allergen (s), but lacks hyperreactive nasal symptoms, (2) one who has IgE specific for an allergen (s) and hyperreactive nasal symptoms, i.e. nasal allergy, (3) one who is negative for IgE specific for an allergen (s), but has hyperreactive nasal symptoms, i.e. vasomotor rhinitis. The numbers of patients were (1) 23, (2) 20, and (3) 5. DNA was extracted from their blood after an informed consent was obtained, and subjected to analysis of genetic polymorphisms in the coding regions of those genes. The combination of polymerase chain reaction (PCR) and single strand comformation polymorphism (SSCP) analysis allowed us to identify a polymorphism of H1 receptor gene at a codon 349 (GAT*CAT,Asp349*His349) in a patient in the group (l). She had the polymorphism in a heterogenous manner. Although it may contribute to hyporeactivity of the nose in the patient, the significance of the polymorphism was considered still little for its low frequency in the population. In terms of NK1 receptor gene, two silent mutations were identified in exonsl and 5, respectively. The former was at a codon 111(TTC*TTT,Phe111), and the latter was at codon 378 (TCG*TCA,Ser378). Because these genetic polymorphisms do not change the structure of NK1 receptor, they have no significance in the pathogenesis of nasal hyperreactivity of the nose. Another study to screen for a mutation in the promoter regions of those genes will be performed hereafter