β2 肾上腺素能受体基因多态性与支气管哮喘：与疾病风险、严重程度和治疗反应的关系。
Beta 2 Adrenergic Receptor Genetic Polymorphisms in Bronchial Asthma: Relationship to Disease Risk, Severity, and Treatment Response.
机构信息
Chest Department, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt.
Department of Histology & Cell Biology, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt.
出版信息
Lung. 2018 Dec;196(6):673-680. doi: 10.1007/s00408-018-0153-3. Epub 2018 Sep 3.
BACKGROUND
The β-adrenergic receptor gene is one of the most extensively studied genes with respect to asthma prevalence and severity. The Arg16Gly and Gln27Glu polymorphisms in the β-adrenergic receptor gene cause changes in the amino acids sequence of the receptor which may cause alteration in response to bronchodilators and the risk of asthma.
OBJECTIVE
The purpose of the study was to determine the association between β-adrenergic receptor gene polymorphisms and asthma risk, severity and response to therapy.
SUBJECTS AND METHODS
58 asthmatic patients and 38 healthy subjects were included. The β-adrenergic receptor polymorphisms genotyping was done using Real-Time polymerase chain reaction.
RESULTS
The allelic frequencies for the Arg16Gly polymorphism were 15.5%, 48.3%, and 36.2% for the homozygous A wild, heterozygous, and homozygous G mutant alleles in asthmatics (P < 0.01) and 5.3%, 47.4%, and 47.4% in healthy subjects (P < 0.01). For the Gln27Glu polymorphism, the allelic frequencies for the homozygous C wild, heterozygous and homozygous G mutant alleles were 51.7%, 41.4%, and 6.9% in asthmatics (P < 0.01) and 44.7%, 39.5%, and 15.8% in healthy subjects (P < 0.01). The heterozygous Arg16Gly and Gln27Glu were found in most of severe asthma cases (7/13, 53.8% each). While homozygous wild and mutant seemed to be protective and associated with mild disease in both alleles. Finally, 75% of Arg16Gly heterozygous group were good responders (P < 0.01), 81% of homozygous G mutant were bad responders. For Gln27Glu polymorphism, 60% of C wild group were good responders and 75% of G mutant group were bad responders.
CONCLUSIONS
The findings suggest that the Arg16Gly and Gln27Glu polymorphisms in the β2-AR gene are associated with asthma severity and response to therapy and might be used in personalized treatment for these patients in the future. This work is registered in ClinicalTrial.gov with ID: NCT03118869.
背景
β-肾上腺素能受体基因是研究哮喘发病率和严重程度最广泛的基因之一。β-肾上腺素能受体基因中的 Arg16Gly 和 Gln27Glu 多态性导致受体氨基酸序列发生变化，可能导致对支气管扩张剂的反应改变和哮喘风险增加。
目的
本研究旨在确定β-肾上腺素能受体基因多态性与哮喘风险、严重程度和治疗反应之间的关系。
受试者和方法
纳入 58 例哮喘患者和 38 例健康对照者。采用实时聚合酶链反应法检测β-肾上腺素能受体基因多态性。
结果
哮喘患者 Arg16Gly 多态性的等位基因频率分别为纯合野生型 A 等位基因 15.5%、杂合型和纯合突变型 G 等位基因 48.3%和 36.2%（P<0.01），健康对照组分别为 5.3%、47.4%和 47.4%（P<0.01）。Gln27Glu 多态性的等位基因频率分别为纯合野生型 C 等位基因 51.7%、杂合型和纯合突变型 G 等位基因 41.4%和 6.9%（P<0.01），健康对照组分别为 44.7%、39.5%和 15.8%（P<0.01）。13 例重症哮喘患者中，7 例（53.8%）为杂合型 Arg16Gly 和 Gln27Glu，2 例（15.4%）为纯合突变型 G。杂合型和纯合野生型似乎具有保护作用，与两种等位基因的轻度疾病相关。最后，Arg16Gly 杂合组中 75%为良好反应者（P<0.01），纯合突变型 G 组中 81%为不良反应者。Gln27Glu 多态性中，C 野生组 60%为良好反应者，G 突变组 75%为不良反应者。
结论
这些发现表明，β2-AR 基因的 Arg16Gly 和 Gln27Glu 多态性与哮喘严重程度和治疗反应有关，可能用于未来这些患者的个体化治疗。本研究在 ClinicalTrials.gov 注册，编号为 NCT03118869。
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