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The Association between

2-Adrenoceptor Polymorphisms

and Asthma

Presented byParichat Lekkhaeng, Pharm. D.

Pharmacy Department of Police General Hospital

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Sites of Action of2-Adrenoceptor

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2-adrenergic agonist

SalmeterolFormoterol

Short acting 2 agonists

Long acting 2 agonists

Salbutamol (Albuterol)TerbutalineFenoterolProcaterol

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Pharmacology

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BRONCHUSΒeta-2 adrenergic receptor

Βeta-2 adrenergic receptor agonist

BRONCHODILATE

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2-Adrenoceptor structure

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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

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Wild type

16 allele

27 allele

Gly/Gly

Glu/Glu

Normal receptor expression

Arg/Gly

Receptor Downregulation

Gln/Glu

Normal Receptor Expression

Polymorph

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Genotype frequencies ofthe Arg/Gly16 polymorphism

Ref.: Thakkinstian A. Et al. Am J Epidemiol 2005;162:201–11.

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Genotype frequencies ofthe Gln/Glu27 polymorphism

Ref.: Thakkinstian A. Et al. Am J Epidemiol 2005;162:201–11.

Page 11Ref.: Thakkinstian A. Et al. Am J Epidemiol 2005;162:201–11.

Genetic effects of Arg/Gly16 andGln/Glu27 polymorphism

ns

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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.: Thakkinstian A. Et al. Am J Epidemiol 2005;162:201–11.

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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.: Thakkinstian A. Et al. Am J Epidemiol 2005;162:201–11.

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β2-receptor polymorphisms(Gln/Glu27) in asthma

In Children Overall was not significant.

Ref.: Thakkinstian A. Et al. Am J Epidemiol 2005;162:201–11.

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Genetic effects of Arg/Gly16 andGln/Glu27 polymorphism

Children AdultAllele 16Gly/Gly 29 % NSArg/Gly - NSArg/Arg - NSAllele 27Glu/Glu NS -Gln/Glu NS 27 % Gln/Gln NS -

Ref.: Thakkinstian A. Et al. Am J Epidemiol 2005;162:201–11.

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Distribution of β2-Adrenoceptor polymorphisms in

Thai asthmatic patients

Ref.: Limsuwan T. Et al. Asian Pac J Allergy Immunol 2010;28:107-14.

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Effects of β2-Adrenoceptor polymorphisms in

Thai asthmatic patients

Gln/Glu Gln/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.

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Distribution of β2-Adrenoceptor polymorphisms in

Thai asthmatic patientsThe presence of the

Glu27 allele in Thai asthmatic patients is associated with Asthma severity

%FEV1 values

frequent hospitalizations and emergency visits

ICS/LABA usageRef.: Limsuwan T. Et al. Asian Pac J Allergy Immunol 2010;28:107-14.

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Thank youFor

Attention

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Distribution of β2-Adrenoceptor polymorphisms in

Thai asthmatic patients

Ref.: Limsuwan T. Et al. Asian Pac J Allergy Immunol 2010;28:107-14.

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Distribution of β2-Adrenoceptor polymorphisms in

Thai asthmatic patientsThe 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.