Hussein Mohammad H, Sobhy Khaled E, Sabry Irene M, El Serafi Ahmed T, Toraih Eman A
Department of Chest Diseases, Faculty of Medicine, Cairo University, Giza, Egypt; Department of Respiratory Medicine, Jahra Hospital, Kuwait.
Department of Chest Diseases, Faculty of Medicine, Cairo University, Giza, Egypt.
Adv Med Sci. 2017 Mar;62(1):193-201. doi: 10.1016/j.advms.2016.07.008. Epub 2017 Mar 17.
Chronic obstructive pulmonary disease (COPD) is a multi-factorial disorder caused by environmental determinants and genetic risk factors. Understanding the genetic predisposition of COPD is essential to develop personalized treatment regimens. Beta-adrenergic receptor (ADRB2) gene polymorphisms have been implicated in the pathogenesis of obstructive pulmonary diseases. This study was conducted to assess the genetic association between Arg16Gly and Gln27Glu polymorphisms and COPD in the Egyptian patients, and to analyze their impact on the clinical outcome and therapeutic response.
PATIENTS/METHODS: The study population included 115 participants (61 COPD patients and 54 healthy controls) were genotyped for the Arg16Gly (rs1042713) and Gln27Glu (rs1042714) polymorphisms. Pulmonary function test was done and repeated in patients after salbutamol inhalation.
The Gly and Gln alleles represented 57% and 70% of the whole study population, and only 3 haplotypes were detected; Arg/Gln, Gly/Gln, and Gly/Glu. Genotypes and haplotypes homozygous for Arg and Gln were more likely to develop COPD (p<0.05). However, individuals carrying Glu allele conferred protection against COPD development (p=0.002). Furthermore, Arg genotypes and haplotypes were significantly associated with higher grades of dyspnea, more COPD symptoms and frequent exacerbations. In contrast, patients carrying Glu allele had better bronchial airway responsiveness to β-agonists.
Our findings suggested that the ADRB2 gene polymorphisms may have vital role in COPD risk, severity, and bronchodilator response among Egyptian population. Larger epidemiological studies are needed for results validation.
慢性阻塞性肺疾病（COPD）是一种由环境决定因素和遗传风险因素引起的多因素疾病。了解COPD的遗传易感性对于制定个性化治疗方案至关重要。β-肾上腺素能受体（ADRB2）基因多态性与阻塞性肺疾病的发病机制有关。本研究旨在评估埃及患者中Arg16Gly和Gln27Glu多态性与COPD之间的遗传关联，并分析它们对临床结局和治疗反应的影响。
患者/方法：研究人群包括115名参与者（61例COPD患者和54名健康对照），对其进行了Arg16Gly（rs1042713）和Gln27Glu（rs1042714）多态性的基因分型。对患者进行了肺功能测试，并在吸入沙丁胺醇后重复测试。
Gly和Gln等位基因分别占整个研究人群的57%和70%，仅检测到3种单倍型；Arg/Gln、Gly/Gln和Gly/Glu。Arg和Gln纯合的基因型和单倍型更易患COPD（p<0.05）。然而，携带Glu等位基因的个体对COPD的发生具有保护作用（p=0.002）。此外，Arg基因型和单倍型与更高程度的呼吸困难、更多的COPD症状和频繁发作显著相关。相比之下，携带Glu等位基因的患者对β-激动剂的支气管气道反应性更好。
我们的研究结果表明，ADRB2基因多态性可能在埃及人群的COPD风险、严重程度和支气管扩张剂反应中起重要作用。需要更大规模的流行病学研究来验证结果。
