Implication of Beta2-Adrenergic and IgE Receptor Polymorphisms in the Susceptibility and Therapeutic Responses of Childhood Asthma in Taiwan

• Main Authors: I-Chun Chou, 周怡君
• Other Authors: Yunn-Fang Ho
• Format: Others
• Language: zh-TW
• Published: 1999
• Online Access: http://ndltd.ncl.edu.tw/handle/48635176884147833326

碩士 === 國立臺灣大學 === 藥學研究所 === 87 === The development of asthma is determined by complex interactions between genetic and environmental factors. Recently, several studies indicated the associations of genetic polymorphisms and asthma. It was postulated that polymorphisms of β2-adrenoceptor may influence the therapeutic responses of asthmatics toβ2-agonists, and polymorphisms of beta chain of the high-affinity immunoglobulin E receptor (FcεRI-β) may play a role in regulating total IgE level. The purpose of this study, therefore, was to evaluate the effects ofβ2-adrenoceptor polymorphism (codon 16 and codon 27) on bronchodilatation response to a single dose of terbutaline, as well as evaluating the effects of FcεRI-βpolymorphism (E237G) on IgE regulation and the associations of these 3 polymorphisms and asthma susceptibility among pediatric asthmatics in Taiwan. One hundred fifty-four asthmatic patients were enrolled from the Pediatric Allergic Special Clinic of National Taiwan University Hospital, and 150 controls were collected from two elementary schools and a junior high school in Taipei via a questionnaire screening. Genomic DNA was isolated from buccal mucosa. We genotyped the polymorphisms of codon 16, codon 27 ofβ2-adrenoceptor and E237G of FcεRI-β by using PCR based RFLP and DNA sequencing. Airway responses (delta forced expiratory volume in one second, △FEV1; pre-inhalation vs. 15 min post-inhalation) to 0.5 mg terbutaline inhalation were examined among 95 asthmatics and 102 controls. Furthermore, we analyzed the association between E237G polymorphism and IgE levels in 131 asthmatic patients. Our results showed, in questionnaire survey, there were 13% , 20% in boys and 11%, 10% in girls who were diagnosed or suspected to have asthma, respectively. The frequency distribution of codon 16, in terms of Arg/Arg: Arg/Gly: Gly/Gly, was 34.7: 48.0: 17.3 for controls, and 28.6: 49.4: 22.1 for asthmatics. The frequency distribution of codon 27, in terms of Gln/Gln: Gln/Glu: Glu/Glu, was 90.0: 9.3: 0.7 for controls, and 85.1: 14.9: 0 for asthmatics. There is no significant difference in frequency distribution between asthmatics and controls. Subgroup univariate analysis showed that among boys, when the number of Gly allele in codon 16 increased, the relative risk increased. Odds ratio of Arg/Gly was 1.46 (95% confidence interval 0.77~2.76, p =0.242), Gly/Gly was 2.58 (95% confidence interval 1.07~6.25, p=0.033). Airway responses (△FEV1) showed no significant difference for codon 16 or codon 27 in our study. However, when the number of Gly allele in codon 16 increased, △FEV1 decreased, it implied the decline of therapeutic response. The frequency distribution of Fcε-RI E237G, in terms of Glu/Glu: Glu/Gly: Gly/Gly, was 82.7: 15.3: 2.0 for controls, and 73.4: 25.3: 1.3 for asthmatics. E237G non-wild type genotype was borderline significant higher in asthmatics than that in controls (odds ratio=1.73, 95% confidence interval 1.0~3.01, p=0.051). However, if we compared the patients with higher total IgE level and allergen specific IgE level to the patients with lower level, the frequency of E237G non-wild type genotype was significantly higher in the higher group (p=0.008). In conclusion, our study showed that the codon 16 ofβ2-adrenoceptor might be a susceptibility risk factor for developing asthma among boys in Taiwan. Genetic polymorphism at codon 16 or codon 27 ofβ2-adrenoceptor did not directly influence stimulated coupling of β2-adrenoceptor. Besides, genetic polymorphism at E237G Fcε-RI may play a role in the pathogenesis of asthma, probably through the regulation of total IgE or allergen specific IgE levels. To understand the actual mechanism of these polymorphisms, further studies are needed.