ADRB2 基因多态性可调节支气管扩张剂的反应和囊性纤维化的严重程度。
Polymorphisms in ADRB2 gene can modulate the response to bronchodilators and the severity of cystic fibrosis.
机构信息
Department of Pediatrics, School of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
出版信息
BMC Pulm Med. 2012 Sep 5;12:50. doi: 10.1186/1471-2466-12-50.
BACKGROUND
The most common cystic fibrosis (CF) manifestation is the progressive chronic obstructive pulmonary disease caused by deficiency, dysfunction, or absence of the CFTR (Cystic Fibrosis Transmembrane Regulator) protein on the apical surface of the cells in the respiratory tract. The use of bronchodilators (BD), and inhaled corticosteroids (IC) have been suggested for the management of airway inflammation in CF. The effectiveness of BD and IC have been verified, proven in laboratory and in the clinical treatment for asthma patients. However, in CF, the effectiveness of these drugs is controversial. The extent of asthma's response to BD depends on the presence of polymorphisms in the ADRB2 gene. In contrast, in CF, little is known about the response to the BD and the association of CF´s severity with the different polymorphisms in ADRB2 gene. In this context, our objective was to verify whether the Arg16Gly and Glu27Gln polymorphisms in ADRB2 gene are associated with severity and with the bronchodilator response in CF patients.
METHOD
Cross-sectional study of 122 CF patients subjected to analysis of mutations in the CFTR gene, polymorphisms in ADRB2 gene, along with clinical and laboratorial characteristics of severity.
RESULT
The Arg16Gly polymorphism in ADRB2 gene was associated with pancreatic insufficiency(p:0.009), Bhalla score(p:0.039), forced expiratory volume in the first secondFEV1(%), forced expiratory flow between 25 and 75% of the forced vital capacity-FVCFEF25-75(%) and lower age at the first isolation of the Pseudomonas aeruginosa(p:0.012). The response to the BD spirometry was associated with clinical severity markers, FEV1(%)(p:0.011) and FEF25-75(%)(p:0.019), for the Arg16Gly polymorphism in the ADRB2 gene. The haplotype analysis showed association with the FEV1/FVC marker from the spirometry test, before and after using the BD, with higher values in the group with Gly/Gly and Glu/Glu, respectively, for the Arg16Gly and Gln27Glu polymorphisms. The analysis by MDR2.0 software, showed association with FEF25-75%; the response to Arg16Gly was respondent by 17.35% and Gln27Glu by 6.8% in variation found.
CONCLUSION
There was an association between the Arg16Gly and Gln27Glu polymorphisms in ADRB2 gene with CF´s severity and bronchodilator response.
背景
最常见的囊性纤维化（CF）表现为由于呼吸道细胞顶表面 CFTR（囊性纤维化跨膜调节剂）蛋白的缺乏、功能障碍或缺失而导致的进行性慢性阻塞性肺疾病。已经建议使用支气管扩张剂（BD）和吸入皮质类固醇（IC）来管理 CF 中的气道炎症。BD 和 IC 的有效性已在实验室和哮喘患者的临床治疗中得到验证。然而，在 CF 中，这些药物的有效性存在争议。BD 对哮喘的反应程度取决于 ADRB2 基因中存在的多态性。相比之下，在 CF 中，对于 BD 的反应以及 CF 严重程度与 ADRB2 基因中不同多态性的关系知之甚少。在这种情况下，我们的目标是验证 ADRB2 基因中的 Arg16Gly 和 Glu27Gln 多态性是否与 CF 患者的严重程度和支气管扩张剂反应相关。
方法
对 122 例 CF 患者进行 CFTR 基因突变分析、ADRB2 基因多态性以及临床和实验室严重程度特征分析的横断面研究。
结果
ADRB2 基因中的 Arg16Gly 多态性与胰腺功能不全（p：0.009）、Bhalla 评分（p：0.039）、第一秒用力呼气容积[FEV1（%）]（p：0.003）、用力呼气量在用力肺活量的 25%至 75%之间[FEF25-75（%）]（p：0.008）和铜绿假单胞菌首次分离时的年龄较小（p：0.012）相关。BD 肺活量计的支气管扩张剂反应与临床严重程度标志物 FEV1（%）（p：0.011）和 FEF25-75（%）（p：0.019）相关，用于 ADRB2 基因中的 Arg16Gly 多态性。单倍型分析显示与 BD 使用前后的肺活量计测试中的 FEV1/FVC 标志物相关，Arg16Gly 和 Gln27Glu 多态性的 Gly/Gly 和 Glu/Glu 组分别具有更高的值。MDR2.0 软件的分析显示与 FEF25-75%相关；在发现的变异中，Arg16Gly 的反应率为 17.35%，Gln27Glu 的反应率为 6.8%。
结论
ADRB2 基因中的 Arg16Gly 和 Gln27Glu 多态性与 CF 的严重程度和支气管扩张剂反应之间存在关联。
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