Vacca Gabriela, Schwabe Kerstin, Dück Ramona, Hlawa Hans-Peter, Westphal Arite, Pabst Stefan, Grohé Christian, Gillissen Adrian
St. Georg Medical Center, Robert-Koch-Hospital, Leipzig, Germany.
Ther Adv Respir Dis. 2009 Feb;3(1):3-10. doi: 10.1177/1753465809102553.
The beta2-adrenergic receptors are cell surface receptors playing a central role in the pharmacological targeting asthma and chronic obstructive pulmonary disease [COPD]. Recent studies suggest that patients who are homozygous for one of the two important polymorphisms of the beta2-adrenergic receptor [ADRB2] gene at codon 16 (arginine to glycine) and 27 (glutamine to glutamate) may have a reduced response to ss2-agonists. Since smoking patients who are Gly16 homozygotes have an increased risk of airway obstruction we hypothesized that beta2-adrenoreceptor gene polymorphisms may be also a cofounder for COPD development and disease severity.
We investigated 190 COPD patients and 172 healthy volunteers in a case-control study. DNA was isolated from whole blood and beta2-AR gene polymorphisms Arg/Gly16 and Gln/Glu27 were determined using allele-specific polymerase chain reaction [PCR].
In COPD patients with Gly/Gly16 was found more frequently than in healthy smokers [29.47% COPD versus 18.18% controls, p = 0.026]. All other gene polymorphisms of the ADRB2 gene at codon 16 were equally distributed between groups. ss2-adrenoreceptor gene polymorphisms were neither a cofounder for COPD exacerbations [>or= 3 hospitalizations within the last 3 years] nor for disease severity [FEV1 <or= 30% predicted].
Our study suggests that the Gly16 allele of the beta2-AR gene predisposes to COPD development but not for exacerbation rates and disease severity. In contrast, Gln/Glu27 polymorphism was irrelevant in our COPD cohort.
β2 - 肾上腺素能受体是细胞表面受体,在哮喘和慢性阻塞性肺疾病(COPD)的药物治疗中起核心作用。最近的研究表明,β2 - 肾上腺素能受体(ADRB2)基因密码子16(精氨酸突变为甘氨酸)和27(谷氨酰胺突变为谷氨酸)的两种重要多态性中,纯合子患者对β2 - 激动剂的反应可能降低。由于携带甘氨酸16纯合子的吸烟患者气道阻塞风险增加,我们推测β2 - 肾上腺素能受体基因多态性可能也是慢性阻塞性肺疾病发生发展和疾病严重程度的一个混杂因素。
我们在一项病例对照研究中调查了190例慢性阻塞性肺疾病患者和172名健康志愿者。从全血中提取DNA,并使用等位基因特异性聚合酶链反应(PCR)测定β2 - AR基因多态性Arg / Gly16和Gln / Glu27。
在慢性阻塞性肺疾病患者中,Gly / Gly16的出现频率高于健康吸烟者(慢性阻塞性肺疾病患者为29.47%,对照组为18.18%,p = 0.026)。ADRB2基因密码子16的所有其他基因多态性在两组之间分布均匀。β2 - 肾上腺素能受体基因多态性既不是慢性阻塞性肺疾病急性加重(过去3年内≥3次住院)的混杂因素,也不是疾病严重程度(第一秒用力呼气容积≤预计值的30%)的混杂因素。
我们的研究表明,β2 - AR基因的Gly16等位基因易导致慢性阻塞性肺疾病的发生,但与急性加重率和疾病严重程度无关。相比之下,Gln / Glu27多态性在我们的慢性阻塞性肺疾病队列中无关紧要。