%0 Journal Article
%T Polymorphism of Beta2-Adrenoceptor and Regular Use of Formoterol in Asthma: Preliminary Results
%A Leonello Fuso
%A Alessandra Di Perna
%A Anna Longobardi
%A Andrea Trov¨¦
%A Michela Bisceglia
%A Benedetta F. Bibi
%A Carla Angelozzi
%A Francesco D. Tiziano
%A Raffaele Antonelli Incalzi
%J ISRN Pulmonology
%D 2013
%R 10.1155/2013/280843
%X Polymorphism at codon 16 of the beta2-adrenoceptor (beta2-AR) affects the responsiveness to salmeterol in asthmatics. Data concerning formoterol are more controversial in the literature. The aim of this study was to verify whether homozygous for arginine-16 (ArgArg16) and homozygous for glycine-16 (GlyGly16) genotypes differently influence the long-term responsiveness to formoterol. Twenty-nine patients with mild-to-moderate asthma, in stable clinical conditions, underwent genotyping at codon 16 of the beta2-AR by RFLP-PCR assay. The effects of a 4-week monotherapy with formoterol (12£¿¦Ìg BID) were tested on the peak expiratory flow (PEF) variability and the forced expiratory volume in 1£¿sec (FEV1) slope of the dose-response curve to salbutamol. Variability in PEF significantly increased during the 4-week treatment period in 14 patients with GlyGly16, but not in 15 patients with ArgArg16 and ArgGly16 . The FEV1 slope of the dose-response curve to salbutamol decreased after the 4-week treatment period in GlyGly16, but not in pooled ArgArg16 and ArgGly16 patients. This study provides preliminary evidence that tolerance to formoterol develops more frequently in asthmatics with GlyGly16 genotype. If confirmed in a larger population, this finding might be useful in choosing the bronchodilator therapy on the basis of genetic polymorphism of the beta2-AR. 1. Introduction Genetic factors, mainly the polymorphism at codons 16 and 27 of the beta2-adrenoceptor (beta2-AR) on chromosome 5q31, are known to modulate the bronchodilatory effects of beta2-agonists [1, 2]. In vitro studies performed on peripheral lymphocytes have shown that asthmatics homozygous for glycine-16 (GlyGly16) are more prone to beta2-agonist-induced downregulation than either homozygous for arginine-16 (ArgArg16) or heterozygous (ArgGly16) [3]. Consistent with in vitro findings are the effects of the acute exposure of asthmatics to short-acting beta2-agonists (SABAs) [4, 5]. However, chronic exposure to SABAs or to the long-acting beta2-agonist (LABA) salmeterol resulted in greater desensitisation among ArgArg16 asthmatics [2, 6¨C9] and these patients are also exposed to an increased risk of exacerbations [10]. A study carried out in children with severe asthma exacerbation hospitalized in intensive care unit showed that patients with genotype GlyGly16 had a more rapid and intense response to therapy with inhaled salbutamol compared with patients with other genotypes [11]. Furthermore, GlyGly16 genotype protected from increase in responsiveness to methacholine during regular treatment with the
%U http://www.hindawi.com/journals/isrn.pulmonology/2013/280843/