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Slides of MR's talk (03-05-2013) during the 79th Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) Abstract as published in [3] Genetic receptor polymorphisms can contribute to a more severe and difficult-to-treat disease pattern in asthma [1]. Uncovering connections of genetic variability and variation in drug response could help to optimize and personalize pharmacological therapy e. g. with b2-adrenoceptor-(ADRB2)-agonists [1]. A pathophysiologically relevant cell type in asthma is the neutrophilic granulocyte, and some of the known polymorphisms in the ADRB2 gene have already been associated with a more severe course of the disease in clinical studies [2]. Therefore, in our study we determined concentration-dependent inhibition of formyl-peptide-induced superoxide production of neutrophils by ADRB2-agonists, and, the complete 1,490 bp ADRB2-sequence per individual. The former parameter allowed robust determination of individual pharmacological profiles for the receptor, and the latter parameter allowed mapping of the most common, but also new or rare polymorphisms (also in the flanking 5’ and 3’ untranslated regions of the gene). With the complete data set at hand, 57 healthy subjects will be grouped, e. g. using the pIC50 as benchmark for responsiveness, or by the assessed polymorphisms. This study provides a basis for implementation of individualized therapy in bronchial asthma. References: [1] Ortega VE, HawkinsGA, Peters SP, Bleecker ER (2007)Pharmacogenetics of the beta 2-adrenergic receptor gene. Immunol Allergy Clin North Am 27: 665-684 [2] Chung LP, Waterer G, Thompson PJ (2011)Pharmacogenetics of b2 adrenergic receptor gene polymorphisms, long-acting b-agonists and asthma. Clin Exp Allergy 41:312-326 [3] No authors listed (2013) Abstracts of the 79th Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology. March 5-7, 2013. Halle, Germany. Naunyn Schmiedebergs Arch Pharmacol 386:Suppl 1:S65 |
