β2-adrenergic receptor (β2AR) polymorphism affects albuterol concentration (Cp)-response relationship in asthmatics

J. A. Johnson, Donald Thomason, M. H.N. Mohamed, Timothy Self, L. V. Eberle, J. J. Lima

Research output: Contribution to journalArticle

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Abstract

Purpose: To determine if common polymorphisms of the β2AR (Arg16→Gly16 & Glu27→Glu27) affect the albuterol Cp-response relationship. Sixteen moderate asthmatics who withheld inhaled steroids for 24h and β-agonist for 36h received oral albuterol 8 mg. β2AR genotype was determined by allele specific oligonucleotide hybridization, albuterol Cp by HPLC and FEV1 by spirometry. The median (range) area under the response (%ΔFEV1)-Cp curve (AURC0-12) was greater in Arg16 homozygotes (hmz) than in patients possessing Gly at codon 16 (Gly16 hmz + heterozygotes (htz)) (194 (45 to 237) %*ml/ng vs 30 (-337 to 146) %*ml/ng, respectively, p<0.05). AURC0-12 was similar in Gly16 hmz and htz. Slopes describing rise to peak response were also different based on genotype (Arg 16 hmz: 1.42 %*ml/ng vs Gly16 hmz+htz: 0.55 %*ml/ng, p<0.05). The codon 27 polymorphism had no effect on the albuterol Cp-response relationship. Conclusions: Asthmatics who are Arg16 hmz have a greater response to β2-agonist therapy than asthmatics possessing Gly at codon 16.

Original languageEnglish (US)
Number of pages1
JournalClinical Pharmacology and Therapeutics
Volume65
Issue number2
DOIs
StatePublished - Jan 1 1999

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Albuterol
Homozygote
Adrenergic Receptors
Heterozygote
Codon
Genotype
Spirometry
Oligonucleotides
Alleles
Steroids
High Pressure Liquid Chromatography

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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β2-adrenergic receptor (β2AR) polymorphism affects albuterol concentration (Cp)-response relationship in asthmatics. / Johnson, J. A.; Thomason, Donald; Mohamed, M. H.N.; Self, Timothy; Eberle, L. V.; Lima, J. J.

In: Clinical Pharmacology and Therapeutics, Vol. 65, No. 2, 01.01.1999.

Research output: Contribution to journalArticle

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abstract = "Purpose: To determine if common polymorphisms of the β2AR (Arg16→Gly16 & Glu27→Glu27) affect the albuterol Cp-response relationship. Sixteen moderate asthmatics who withheld inhaled steroids for 24h and β-agonist for 36h received oral albuterol 8 mg. β2AR genotype was determined by allele specific oligonucleotide hybridization, albuterol Cp by HPLC and FEV1 by spirometry. The median (range) area under the response ({\%}ΔFEV1)-Cp curve (AURC0-12) was greater in Arg16 homozygotes (hmz) than in patients possessing Gly at codon 16 (Gly16 hmz + heterozygotes (htz)) (194 (45 to 237) {\%}*ml/ng vs 30 (-337 to 146) {\%}*ml/ng, respectively, p<0.05). AURC0-12 was similar in Gly16 hmz and htz. Slopes describing rise to peak response were also different based on genotype (Arg 16 hmz: 1.42 {\%}*ml/ng vs Gly16 hmz+htz: 0.55 {\%}*ml/ng, p<0.05). The codon 27 polymorphism had no effect on the albuterol Cp-response relationship. Conclusions: Asthmatics who are Arg16 hmz have a greater response to β2-agonist therapy than asthmatics possessing Gly at codon 16.",
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AU - Eberle, L. V.

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