Study the Possib
Study the Possible Role of β2 Adrenergic Receptor Gene in the Pathogenesis of Bronchial Hyperresponsiveness in Asthmatic Patients and its Relation to Disease Severity and Treatment Response
Ibrahim M. El Akkary1, Zenat A. El-Kholy2, Mohamed M. Mokhtar3, Mervat M. Mostafa2, Inas M. Masoud2, and Abdel Nasser I. Adam1
From Departments of Human physiology 1, Applied Medical Chemistry 2, Human Genetics 3, Medical Research Institute, Alexandria University, Egypt. firstname.lastname@example.org
Abstract: Background and objectives: Several identified β2-adrenergic receptor (β2AR) gene polymorphisms, including the amino acid substitution from arginine (Arg) to glycine (Gly) at codon 16 and from glutamine (Gln) to glutamic acid (Glu) at codon 27, are linked with functional changes in the β2AR in the respiratory system. The objective of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in β2AR gene in asthmatic patients with bronchial hyperresponsiveness (BHR), asthma severity, and response to inhaled long acting β2 agonists.Methods: This case-control association study involved 60 patients with asthma and 60 healthy subjects. Thirty asthmatics patients of them received inhaled long acting β2agonists. The β2AR gene polymorphisms at codon 16 and 27 were assessed on the genomic DNA obtained from the whole blood. Genotyping was carried out by a PCR based restriction fragment length polymorphism technique.Results: 1- The combined genotype Gly-Gly/Gln-Glu was positively associated with BHR (P < 0.05). 2- No association between β2AR polymorphism at codon 16 and asthma severity was observed. However; homozygous Gln27 genotype was significantly associated with severe asthma either individually or when combined with homozygous Gly16. In contrast; Glu 27 was found to reduce asthma severity as a significant negative association was observed between Gln-Glu, Gly-Gly/Gln-Glu and clinical severity score, and between Gly-Gly/Gln-Glu and the airway reactivity score (P < 0.05). 3- Glu27Glu genotype had significant positive association with the improvement in BHR (assessed by percentage of change in PD20-FEV1) after long acting β2 agonist administration for 14 days (P <0.05). Conclusions: β2AR gene can confer genetic susceptibility to BHR and the combinations of β2AR genotypes are more informative than individual SNPs in their predictive power. Polymorphisms in β2AR gene are important in the modulation of asthma severity and response to β2 agonist. The predetermination of single β2AR genotypes might have a utility for predicting long-acting β2agonist response.
[I. M. El Akkary, Z. A. El-Kholy, M. M. Mokhtar, M. M. Mostafa, I. M. Masoud, and A.I. Adam. Study the Possible Role of β2 Adrenergic Receptor Gene in the Pathogenesis of Bronchial Hyperresponsiveness in Asthmatic Patients and its Relation to Disease Severity and Treatment Response. J Am Sci 2012;8(10):394-408]. (ISSN: 1545-1003). http://www.jofamericanscience.org. 58
Keywords: Polymorphisms, β2-adrenergic receptor gene, Bronchial hyperresponsiveness. Full Text 58