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，这些受体参与了鼻子高反应性的发展。在这项研究中，我们招募了48名符合以下标准之一的患者：(1)有过敏原特异性IgE，但没有高反应性鼻部症状；(2)有过敏原特异性IgE和高反应性鼻部症状，即鼻过敏；(3)有过敏原特异性IgE阴性，但有高反应性鼻部症状，即血管收缩性鼻炎。患者数为(1)23例，(2)20例，(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域的遗传多态性进行分析。结合聚合酶链反应（PCR）和单链构象多态性（SSCP）分析，我们在该组患者中鉴定出H1受体基因密码子349 （GAT*CAT,Asp349*His349）的多态性(1)。她以异质的方式拥有多态性。虽然它可能会导致患者鼻子的低反应性，但由于其在人群中的低频率，多态性的意义仍然被认为很小。在NK1受体基因方面，分别在外显子sl和5处发现了两个沉默突变。前者位于密码子111位（TTC*TTT,Phe111），后者位于密码子378位（TCG*TCA,Ser378）。由于这些遗传多态性不改变NK1受体的结构，因此在鼻部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域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