糖皮质激素受体基因G679S多态性与激素抵抗型哮喘的相关性  

Association of G679S polymorphism of glucocorticoid receptor gene and steroid-resistance in asthma

作　　者：赵峰[1] 遆新宇[1] 蔡累[1] 王安辉[2] 李志奎[1] 刘颖格[1] 吴昌归[1] 

机构地区：[1]第四军医大学西京医院呼吸内科 [2]第四军医大学预防医学系流行病学教研室,陕西西安710033

出　　处：《第四军医大学学报》2009年第6期541-544,共4页Journal of the Fourth Military Medical University

基　　金：国家自然科学基金(30570803)

摘　　要：目的:检测糖皮质激素受体(Glucocorticoid Recep-tor,GR)基因G679S的多态性,探讨其与激素抵抗型哮喘的相关性.方法:采用聚合酶链反应-序列特异性引物(PCR-SSP)的方法对217例激素敏感型哮喘患者、64例激素抵抗型哮喘患者及221例健康对照组的GR基因G679S进行多态性分析,判断其与激素抵抗、血清皮质醇浓度及GR解离常数(Kd)的相关性.结果:GG型、GA型及AA型基因频率在激素抵抗组分别为46.9%,42.2%,10.9%.与敏感组的63.6%,31.3%,5.1%和对照组的65.6%,29.0%,5.4%的基因频率有显著差异(P=0.035,P=0.02).抵抗组GA+AA基因型及A等位基因频率明显高于其他两组,而抵抗组GA+AA基因型Kd值显著高于GG型(P=0.029).血清皮质醇浓度在各基因型无明显差异.结论:G679S基因多态性与哮喘激素抵抗的产生有关,等位基因A可能是激素抵抗产生的易感基因.AIM： To investigate the association of glucocorticoid receptor （GR） gene G679S polymorphisms and steroid-resistant asthma. METHODS ： G679S polymorphism of GR gene was genotyped in 64 steroid-resistant （SR） asthma patients, 217 steroid- sensitive （SS） asthma patients and 221 healthy control subjects by the PCR sequence specific primer （PCR-SSP） technique. The plasma cortisol levels and GR dissociation constant （Kd） were also detected in all the three groups. RESULTS： It was found that the frequencies of GG, GA and AA genotypes of G679S in SR were 46.9%, 42.2% and 10. 9%, respectively. They were statistically different in the distributions of the genotypes in SS, 63. 6%, 31.3% and 5. 1% and in healthy control subjects, 65. 6%, 29.0% and 5.4%, respectively （P=0.035, P=0.02）. It was also found that GA ＋ AA genotypes and A allele frequencies in SR were significantly higher than those in SS and healthy control subjects. In SR, GR Kd was significantly higher in GA ＋ AA genotypes than that in GG genotype （ P = 0.029 ）. However, there was no significant difference in the plasma cortisol levels in all the three genotypes. CONCLUSION： The G679S gene polymorphism of GR is associated with steroid-resistant asthma and the allele A may be a risk factor for steroid-resistance in Chinese population.

关 键 词：哮喘 受体 糖皮质激素 抵抗 多态现象 遗传 聚合酶链反应-序列特异性引物 

分 类 号：R562.2[医药卫生—呼吸系统]