Tachyphylaxis to β2-agonists in Spanish asthmatic patients could be modulated by β2-adrenoceptor gene polymorphisms

SummaryBackgroundThe study of determinants of asthma is a subject of much interest currently, especially the pharmacogenetic aspects of asthma management. Genetic polymorphisms affecting amino-acids at positions 16 and 27 within β2-adrenoceptor (β2AR) gene have been implicated in the asthma phenotypes and influence on the variability observed in response to use of bronchodilator agents used in the treatment of asthma. Whether these polymorphisms alter the bronchoprotection response to β2β2-agonist treatment in Spanish asthmatic population is unknown. The aim of this study was to investigate whether genetic polymorphisms within β2AR gene modulate the clinical outcomes of the individual response to β2-agonist therapy and the development of desensitization in Spanish asthmatic patients.MethodsIn a prospective, case-control study were included 80 asthmatic patients. Based on the standard criteria, patients were classified into two groups: patients with tachyphylaxis and good responders to β2-agonist therapy. DNA samples were genotyped for the Arg16Gly and Glu27Gln alleles within the β2AR gene as well as in 64 control samples from blood donors.ResultsArg16 allele was slightly more frequent within the group with tachyphylaxis (P=0.039P=0.039), whereas Gly16 allele carriers were overrepresented within the group of good responders (59.7%, P=0.028P=0.028). On the other hand, the allele frequency of Gln27 and the proportion of Gln27 carriers was higher within the group with tachyphylaxis (P=0.010P=0.010 and 0.0490.049, respectively) and Glu27 allele carriers were overrepresented within the group of good responders (P=0.026P=0.026). The Arg16 and Gln27 alleles were in strong linkage disequilibrium across this locus, resulting in the occurrence of disease haplotype.ConclusionsThe predisposition to develop tachyphylaxis in our population seems to be linked to the Arg16 and Gln27 alleles and to the Arg16/Gln27 risk haplotype (positive association between the presence of the Arg16 and Gln27 alleles and tachyphylaxis). The Arg16 allele is perhaps overrepresented due to the strong linkage disequilibrium between both polymorphisms. The presence of the Glu27 allele seems to be a protective factor against tachyphylaxis in this cohort study.