Molecular Pathophysiology of Asthma: Relationship between β2-adrenergic receptor gene polymorphisms and pathophysiology of bronchial asthma

2.使用稳定的ARMS方法，150种健康控制和178种哮喘的基因型。However，在asthmatics中，Gly 16/Gly 16基因型与哮喘的严重程度及其在治疗中的用途有关。在补充中，甲基苯丙胺在治疗中存在着明显的种族差异。在补充中，基因型中存在着明显的种族差异。在日本，Glu 27/Glu 27基因型非常罕见，只有1%的人口具有这种基因型。β 2-肾上腺素受体基因多态性和病理学被测试了，随后的结果也得到了。用于确定核苷酸46、79和523基因型的ARMS方法已被应用于两种测序特定PCR和直接测序方法。同位素诱导的c-AMP反应的外围单核（PMN）细胞被测试。D2在核苷酸46基因型（Arg 16或Gly 16）之间没有差异，以及Gly 16/Gly 16基因型显示相对较弱的最大反应与其他基因型（P<0.1）。2周的影响--用β 2-抗抑郁者在19个哮喘患者中进行了测试。Gly 16/Gly 16基因型患者在治疗后显示出基线FEV 1、PCy-D220-甲基苯丙胺和c-AMP对抑制沙丁胺醇的反应，建议在长期β 2-抗治疗后，受体下调节可能会被诱导，可能会导致这种基因型的哮喘恶化。这些结果建议β 2-肾上腺素受体基因多态性是遗传学背景中的一个，它修改了慢性哮喘的临床特征和β 2-抗治疗的有效性。

2. With the established ARMS methods, genotypes of 150 healthy controls and 178 asthmatics. However, in asthmatics, Gly16/Gly16 genotype was related to the severity of asthma and the use of methylxanthin in their treatment. In addition, there was a significant racial differences in methylxanthin in their treatment. In addition, there was a significant racial differences in genotypes. In Japanese, Glu27/Glu27 genotype is extremely rare and only 1% of population has this genotype.Relationships between β2-adrenergic receptor gene polymorphisms and pathophysiology of bronchial asthma were examined and the following results were obtained.1. The ARMS method for the determination of genotype of nucleotide 46, 79 and 523 was established by applying both sequence specific PCR and direct sequencing with di-deoxi method.3. Isoproterenol induced c-AMP response of peripheral mononuclear (PMN) cells were examined. There was no difference in ECィイD250ィエD2 among nucleotide 46 genotype (Arg16 or Gly16), however, Gly16/Gly16 genotype showed relatively weak maximum response compared to other genotypes (P<0.1).4. The effects of 2 weeks-regular inhalational therapy with β2-agonist were examined in 19 asthmatic patients. Patients with Gly16/Gly16 genotype showed significant decrease in baseline FEV1, PCィイD220ィエD2-methacholine and c-AMP responses to inhaled salbutamol after treatment, suggesting that receptor down-regulation may be induced after long-term β2-agonist therapy and may cause worsening of asthma in this genotype.These results suggest that β2-adrenergic receptor gene polymorphisms are one of the genetic background which modify the clinical characteristics of bronchial asthma and the effectiveness of β2-agonist treatment.