Beta2-adrenergic receptor gene haplotypes and bronchodilator response in Egyptian patients with chronic obstructive pulmonary disease.
OBJECTIVE
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.


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 Gly16and Gln27alleles 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 Arg16and Gln27were more likely to develop COPD (p<0.05). However, individuals carrying Glu27allele conferred protection against COPD development (p=0.002). Furthermore, Arg16genotypes and haplotypes were significantly associated with higher grades of dyspnea, more COPD symptoms and frequent exacerbations. In contrast, patients carrying Glu27allele 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.
Department of Chest Diseases, Faculty of Medicine, Cairo University, Giza, Egypt; Department of Respiratory Medicine, Jahra Hospital, Kuwait. Electronic address: hosny.mh@gmail.com.
Mohammad H
MH
Hussein
Department of Chest Diseases, Faculty of Medicine, Cairo University, Giza, Egypt.
Khaled E
KE
Sobhy
Department of Chest Diseases, Faculty of Medicine, Cairo University, Giza, Egypt.
Irene M
IM
Sabry
Department of Medical Biochemistry, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; Basic Medical Sciences Department, University of Sharjah, Sharjah, United Arab Emirates.
Ahmed T
AT
El Serafi
Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
Eman A
EA
Toraih
D000328:Adult; D000483:Alleles; D015415:Biomarkers / Q000378:metabolism; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D004534:Egypt; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012129:Respiratory Function Tests
C553443:ADRB2 protein, human; D015415:Biomarkers; D001993:Bronchodilator Agents; D018343:Receptors, Adrenergic, beta-2
Bronchodilator response; Egyptian; Single nucleotide polymorphism; qRT-PCR; β(2)-Adrenergic receptor gene