ADRB2 GENE POLYMORPHISMS AND SALBUTAMOL RESPONSIVENESS IN SERBIAN CHILDREN WITH ASTHMA
Jovicic N, Babic T, Dragicevic S, Nestorovic B, Nikolic A
*Corresponding Author: Dr. Nevena Jovicic, Department of Pulmonology and Allergology, University Children’s Hospital, Tirsova 10, 11000 Belgrade, Serbia. Tel: +38-164-115-6721. Fax: +38-111-268-5378. E-mail: jovicic.nevena@gmail.com
page: 33

INTRODUCTION

Inhaled β2 adrenergic receptor (β2-AR) agonists are drugs that form the basis of asthma therapy [1]. They are administered periodically or continuously, and during disease exacerbations. The absence of response to the applied therapy and the occurrence of severe exacerbation of the disease requires admission to the hospital, and in the most severe cases, to the pediatric intensive care unit. Therefore, prediction of response to a specific therapy is of great importance in the treatment of asthma exacerbations in children [2]. The β2-AR is encoded by the ADRB2 gene and its variations can significantly modulate the response to asthma therapy [3]. The ADRB2 gene is located on chromosome 5q31-q32, in a region associated with asthma. Several polymorphisms in the ADRB2 gene have been described [4]. The β2 receptors are present in the respiratory tract, especially in the smooth muscle cells. The most important clinical effect of activation of β2-AR by its agonists is relaxation of the lung smooth muscles. Chronic exposure to the agonists leads to a significant reduction in the number of β2-AR on the surface of the cell [4]. The two most common polymorphisms in the ADRB2 gene are +46A>G (Arg16Gly, rs1042713) and +79C>G (Gln27Glu; rs1042714) [5]. There is evidence that +46A>G and +79C>G polymorphisms alter the functioning of the receptor, leading to down-regulation of β2-AR and thereby induce a resistance to the effect of β2-agonists [6]. A significant correlation was found between the positive therapeutic response to inhaled β2-agonists in children with asthma and +46AA genotype in comparison with +46AG and +46GG genotypes [7,8]. Polymorphism +46A>G can be an important factor in the overall genetic risk of developing asthma, while polymorphism +79C>G is described as a risk factor for asthma in adults in some ethnic groups [9-11]. A previous study in the Serbian population has shown that adult carriers of allele +79C and genotype +79CC are at increased risk of developing asthma [12]. The aim of this study was to analyze the incidence of +46A>G and +79C>G polymorphisms/variants in Serbian children with asthma, and to investigate their influence on the severity of the disease and the response to inhaled β2-agonists.



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