The investigation of beta-2 adrenoceptor (ADRB2) 16 and glutathione S-tranferase P1 (GSTP1)gene polymorphisms in asthma patients

Individual differences, depending on genetic factors, in activity of some enzymes that metabolise xenobiotics have become the subject of several studies in recent years. Especially the genetic polymorphism researhes are important for drug action and drug toxicity. In addition, it?s reported that polymorphisms in xenobiotic metabolism increases the susceptibility to certain disease, especially the cancer, via drug resistance, adverse reactions and xenobiotic exposure. Asthma incidence is determined as 2.65 - 4 / 1000 per year and the prevalence is about 3- 5 %, 5-10 % in adults and in childhood, respectively. In United States, it?s observed in 4 % of general population. It?s also reported that there are 10 million patients with asthma in States and the asthma is the 13th most common disease in the applications for medical medical care. It?s believed that genetic factors play the major role in etiological and phenotypical properties of asthma. Hence, the individual differences in the functions of bronchial ß2 adrenoceptors (ADRB2) and individual differences in glutathione S-transferase P1 (GSTP1) metabolism may affect the incidence of asthma in population. In recent years, ADRB2 16 and GSTP1 gene polymorphisms are studied in different populations. After completion of Human Genome Project to reach reliable datas in gene- diseases relationship, studies are designed in different populations and with larger sample sizes to make meta-analysis possible. Assesment of relationship between pathology of asthma and ADRB2 16 and GSTP1 polymorphism in Turkish population gains importance because of this reason. ADRB2 is a functional G coupled-protein couple found especially in vascular endothelium of lungs, alveolar walls, ganglions of cholinergic nerves, which causes bronchodilation in response to catecholamines. ADRB2 gene is located at 5q31.32 locus on long arm of chromosome 5 and encoded by one exon. ADRB2 16 polymorphism is identified by which Arginin (Arg) is substituted by Glycine (Gly) at the nucleotide 46 in the codon 16. GSTP1 is a candidate pi class GST gene which controls pi class glutathione S- transferase activity. It?s located on the arm of choromosome 11q13 which is associated with the atopia and airway sensitivity it contains 7 exons. GSTP1 polymorphism is defined by which Isoleucine (Ile) is substituted by Valine (Val) at the exon 5, and codon 105. In this study, 129 asthmatic patients and 127 healthy control cases were recruited to determine ADRB2 and GSTP1 genotypes using Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) methods. The ADRB2 genotype frequencies of the patients and control cases were found to be; 10,9 % (Arg16Arg), 48,8 % (Arg16Gly), 40,3 % (Gly16Gly); and 24,4 % (Arg16Arg), 36,2 % (Arg16Gly), 39,4 % (Gly16Gly), respectively. ADRB2 allele frequencies of patients and control cases were; 35,3 % (Arg 16) 64,7 (Gly16); 42,5 % (Arg16), 57,5 (Gly16). GSTP1 genotype frequencies of patients and control cases were found to be; 55 % (Ile105Ile), 43,4 % (Ile105Val), 1,6 % (Val105Val); and 75,6 % (Ile105Ile), 22% (Ile105Val), 2,4 % (Val105Val) respectively. The allele frequencies were found as 76,5 % (Ile105), 23,3 % (Val105); 86,6 % (Ile105), 13,4 % (Val105). In the cases of ADRB2 gene, we did not observe any significant difference between cases and controls, whereas we found a statistically significant difference in the genotype frequency of Ile105Val and the allele frequency of Val105 in asthmatic group compared to controls. Moreover, we observed a relation between allele frequencies and phenotypical properties like atophia, nocturnal dyspnea and steroid depency in the asthmatic patients.