1. Page 1 The Association between  2 -Adrenoceptor Polymorphisms and Asthma Presented by Parichat Lekkhaeng, Pharm. D. Pharmacy Department of Police General Hospital

2. Page 2 Fig.3 Sites of Action of  2 -Adrenoceptor Sites of Action of  2 -Adrenoceptor

3. Page 3  2 -adrenergic agonist Salmeterol Formoterol  Short acting  2 agonists  Long acting  2 agonists Salbutamol (Albuterol) Terbutaline Fenoterol Procaterol

4. Page 4 Pharmacology

5. Page 5 BRONCHUS Βeta-2 adrenergic receptor Βeta-2 adrenergic receptor agonist BRONCHODILATE

6. Page 6  2 -Adrenoceptor structure

7. Page 7 β 2 - receptor polymorphisms in asthma  Two common polymorphisms:  Arg/Gly16 (Gly/Gly16)  Gln/Glu27 (Glu/Glu27)  In vitro studies:  Arg/Gly16 allele   induce to down regulation  Gln/Glu27 allele   resistance to down regulation

8. Page 8 Wild type 16 allele 27 allele Gly/Gly Glu/Glu Normal receptor expression Arg/Gly Receptor Downregulation Gln/Glu Normal Receptor Expression Polymorph

9. Page 9 Genotype frequencies of the Arg/Gly16 polymorphism Ref.: Thakkinstian A. Et al. Am J Epidemiol 2005;162:201–11.

10. Page 10 Genotype frequencies of the Gln/Glu27 polymorphism Ref.: Thakkinstian A. Et al. Am J Epidemiol 2005;162:201–11.

11. Page 11 Ref.: Thakkinstian A. Et al. Am J Epidemiol 2005;162:201–11. Genetic effects of Arg/Gly16 and Gln/Glu27 polymorphism ns

12. Page 12 β 2 - receptor polymorphisms (Arg/Gly16) in asthma  In Adult  Overall was not significant.  In Children  The estimated odds ratio was 0.71 (95%CI: 0.53, 0.96)  Gly/Gly  29%  risk of asthma  Arg/Arg  Arg/Gly Ref.: Thakkinstian A. Et al. Am J Epidemiol 2005;162:201–11.

13. Page 13 β 2 - receptor polymorphisms (Gln/Glu27) in asthma  In Adult  Heterozygotes  risk of asthma than either homozygote.  Pooling: odds ratio was 0.73 (95%CI: 0.62, 0.87)  Gln/Glu genotype  27%  risk of asthma  Gln/Gln  Glu/Glu Ref.: Thakkinstian A. Et al. Am J Epidemiol 2005;162:201–11.

14. Page 14 β 2 - receptor polymorphisms (Gln/Glu27) in asthma  In Children  Overall was not significant. Ref.: Thakkinstian A. Et al. Am J Epidemiol 2005;162:201–11.

15. Page 15 Genetic effects of Arg/Gly16 and Gln/Glu27 polymorphism ChildrenAdult Allele 16 Gly/Gly 29 % NS Arg/Gly-NS Arg/Arg-NS Allele 27 Glu/GluNS- Gln/GluNS 27 % Gln/GlnNS- Ref.: Thakkinstian A. Et al. Am J Epidemiol 2005;162:201–11.

16. Page 16 Distribution of β 2 -Adrenoceptor polymorphisms in Thai asthmatic patients Ref.: Limsuwan T. Et al. Asian Pac J Allergy Immunol 2010;28:107-14.

17. Page 17 Effects of β 2 -Adrenoceptor polymorphisms in Thai asthmatic patients Gln/GluGln/Gln Hospitalizations (p= 0.122) 0%11.9% Emergency visits (p = 0.121) 4.5%18.8% ICS/ LABA usages(p = 0.042) 50%76.6% Ref.: Limsuwan T. Et al. Asian Pac J Allergy Immunol 2010;28:107-14.

18. Page 18 Distribution of β 2 -Adrenoceptor polymorphisms in Thai asthmatic patients  The presence of the Glu27 allele in Thai asthmatic patients is associated with   Asthma severity   %FEV1 values   frequent hospitalizations and emergency visits   ICS/LABA usage Ref.: Limsuwan T. Et al. Asian Pac J Allergy Immunol 2010;28:107-14.

19. Page 19 Thank you For Attention

20. Page 20 Distribution of β 2 -Adrenoceptor polymorphisms in Thai asthmatic patients Ref.: Limsuwan T. Et al. Asian Pac J Allergy Immunol 2010;28:107-14.

21. Page 21 Distribution of β 2 -Adrenoceptor polymorphisms in Thai asthmatic patients  The mean percentages for predicted FEV1 (%FEV1)  Arg-Gln 73.5 (SD = 16.3)  Gly-Gln 72.4 (SD = 17.4)  Gly-Glu 80.7 (SD = 13.1)  p = 0.258 Ref.: Limsuwan T. Et al. Asian Pac J Allergy Immunol 2010;28:107-14.