Purpose: 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. Beta₂-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.

Results: The Gly₁₆ and Gln₂₇ alleles represented 57% and 70% of the whole study population, and only 3 haplotypes were detected; Arg₁₆/Gln₂₇, Gly₁₆/Gln₂₇, and Gly16/Glu27. Genotypes and haplotypes homozygous for Arg16 and Gln₂₇ were more likely to develop COPD (p<0.05). However, individuals carrying Glu27 allele conferred protection against COPD development (p=0.002). Furthermore, Arg₁₆ genotypes and haplotypes were significantly associated with higher grades of dyspnea, more COPD symptoms and frequent exacerbations. In contrast, patients carrying Glu₂₇ allele had better bronchial airway responsiveness to β2-agonists.

Conclusions: 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.