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The Association between  2 -Adrenoceptor Polymorphisms and Asthma

The Association between  2 -Adrenoceptor Polymorphisms and Asthma. Presented by Parichat Lekkhaeng , Pharm. D. Pharmacy Department of Police General Hospital. Sites of Action of  2 - Adrenoceptor. Fig.3 Sites of Action of  2 - Adrenoceptor.  2 -adrenergic agonist. Salmeterol

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The Association between  2 -Adrenoceptor Polymorphisms and Asthma

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

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

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

  4. Pharmacology

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

  6. 2-Adrenoceptor structure

  7. β2-receptor polymorphismsin 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. Wild type Polymorph 16 allele Gly/Gly Arg/Gly 27 allele Glu/Glu Gln/Glu Normal Receptor Expression Normal receptor expression Receptor Downregulation

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

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

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

  12. β2-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.: ThakkinstianA. Et al. Am J Epidemiol 2005;162:201–11.

  13. β2-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.: ThakkinstianA. Et al. Am J Epidemiol 2005;162:201–11.

  14. β2-receptor polymorphisms(Gln/Glu27) in asthma • In Children • Overall was not significant. Ref.: ThakkinstianA. Et al. Am J Epidemiol 2005;162:201–11.

  15. Genetic effects of Arg/Gly16 andGln/Glu27 polymorphism Ref.: ThakkinstianA. Et al. Am J Epidemiol 2005;162:201–11.

  16. Distribution of β2-Adrenoceptor polymorphisms inThai asthmatic patients Ref.: Limsuwan T. Et al. Asian Pac J Allergy Immunol 2010;28:107-14.

  17. Effects of β2-Adrenoceptor polymorphisms inThai asthmatic patients Ref.: Limsuwan T. Et al. Asian Pac J Allergy Immunol 2010;28:107-14.

  18. Distribution of β2-Adrenoceptor polymorphisms inThai 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. Thank you For Attention

  20. Distribution of β2-Adrenoceptor polymorphisms inThai asthmatic patients Ref.: Limsuwan T. Et al. Asian Pac J Allergy Immunol 2010;28:107-14.

  21. Distribution of β2-Adrenoceptor polymorphisms inThai 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.

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