Correlation study on beta 2-adrenergic receptor gene polymorphisms and asthma susceptibility: evidence based on 57 case-control studies
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES
Authors: Yu, X.; Wang, L-W; He, Q.; Khan, K.; Chen, X-Y; Li, J.
Abstract
OBJECTIVE: Previous studies have indicated that beta 2-adrenergic receptor (ADRB2) genetic polymorphism is related to the risk of asthma, but the results still have some controversy and uncertainty. To this end. the meta-analysis was performed. including all studies that can be used to assess the correlation between ADRB2 polymorphism and asthma susceptibility. MATERIALS AND METHODS: The related papers on ADRB2 polymorphisms and asthma were systematically reviewed in databases of PubMed, EMBASE, Cochrane Library, and Wan-Fang, Odds ratios (ORs) and corresponding 95% confidence intervals (95% Cls) were measured. The sensitivity analysis and publication bias were evaluated to investigate the correlation. RESULTS: This meta-analysis included 57 papers in total involving 11,157 cases and 12,281 controls. Results illustrated that the C79G variant genotypes owned a reduced effect on asthma susceptibility (G vs. C: OR=0.94, p=0.037). In the age stratification analysis, C79G polymorphism owned a reduced effect on asthma risk for children (GG vs. CC: OR=0.69, p=0.002; GG vs. CC+CG: OR=0.65, p<0.001). Furthermore, in the ethnic stratification analysis, the C79G variant genotypes also owned a reduced effect on asthma in Asians (GG vs. CC: OR=0.80, p=0.027; GG vs. CC+CG: OR=0.81, p=0.02). Besides, for A46G polymorphism. the ethnic stratification analysis demonstrated that the A46G variant owned an increased effect on asthma susceptibility among Caucasians (G vs. A: OR=1.15, p=0.043). For C491T polymorphism, a considerable reduced effect was found between C491T and asthma susceptibility for children (CT vs. CC: OR=0.70, p=0.03). In the ethnic stratification analysis, the effect was also considerable in the Caucasian subjects. CONCLUSIONS: The present meta-analysis demonstrated that C79G and C491T polymorphism may be a defensive factor for asthma, while A46G polymorphism may be a risk factor for asthma among the Caucasian population.
Do genetic polymorphisms alter patient response to inhaled bronchodilators?
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
Authors: Lima, John J.
Abstract
Introduction: Short- and long-acting beta agonists (SABA and LABA) are bronchodilators for treating asthma. Bronchodilator response (BDR) is quantified by measuring air expired in the first second during a forced expiratory maneuver, prior to and following inhalation of SABA. BDR has been associated with a significant degree of heterogeneity, in part attributable to genetic variation. Heritability, the proportion of phenotypic variability accounted for by genetic variation is estimated to account for 50% of pulmonary function and 28.5% for BDR. Areas covered: A MEDLINE search for English articles published from January 1990 to June 2014 was completed using the terms: bronchodilator, bronchodilator response, short-acting bronchodilator, long-acting bronchodilator, beta 2 adrenergic receptor gene (ADRB2), asthma and pharmacogenomics. The effects of ADRB2 variants on BDR and the safety of SABA and LABA + inhaled corticosteroids have been studied with equivocal results. Single and candidate gene studies have identified variants in other genes that alter response to bronchodilators. Associations were recently observed between hospital admission rates and two rare ADRB2 polymorphisms: Thr164Ile and a 25 base pair insertion-deletion at nucleotide -376. This was the first report of life-threatening events associated with LABA being linked to rare ADRB2 variants. Expert opinion: Pharmacogenomic studies over the last two decades clearly demonstrate that polymorphisms alter patient response to bronchodilators in patients with asthma.