Association of Beta 2 adrenergic receptor (Thr164Ile) polymorphism with Salbutamol refractoriness in severe asthmatics from Indian population

Gene. 2016 Oct 30;592(1):15-22. doi: 10.1016/j.gene.2016.07.043. Epub 2016 Jul 20.

Abstract

Background: Thr164Ile polymorphism in the ADRB2 gene encoding β2 adrenergic receptor (β2AR) has its functional consequence in declining ligand-receptor interactions and depressed coupling of β2AR to adenylcyclase. In the present study, we sought to evaluate the possible association of Thr164Ile polymorphism with asthma susceptibility, pharmacogenetic response to Salbutamol and varying degrees of severity.

Methods: Three hundred and ninety eight clinically diagnosed patients and four hundred and fifty six healthy controls were enrolled in the study. Patients were classified into severity classes according to the Global Initiative for Asthma (GINA) guidelines. To assess bronchodilator response, spirometry was performed before and 15min after Salbutamol (200μg) delivery. Responders to Salbutamol were categorized if percentage reversibility was greater than or equal to 12% in them, while those showing reversibility <12% were classified as non-responders. Further, responding phenotypes were stratified into severity groups. Genotyping was carried out by ARMS-PCR technique. Statistical methods were applied to test the significance of the results.

Results: In the present study, polymorphism was not associated with disease susceptibility however; there was significant association with non-responding asthmatics. In case of severity subsets, the polymorphism was not associated with milder subtypes; although, notable association was observed with moderate and severe asthma subtypes. In addition, the polymorphism was significantly associated with non-responding patients with severe asthma.

Conclusions: In south Indian population, the ADRB2 Thr164Ile polymorphism may not form susceptible variant to develop asthma, however, it can form a predictive maker for bronchodilator (Salbutamol) response in severe asthmatics.

Keywords: Asthma severity; Bronchial asthma; Salbutamol refractoriness; Thr164Ile polymorphism.

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / pharmacology
  • Adrenergic beta-2 Receptor Agonists / therapeutic use*
  • Adult
  • Albuterol / pharmacology
  • Albuterol / therapeutic use*
  • Asthma / drug therapy
  • Asthma / genetics*
  • Bronchodilator Agents / pharmacology
  • Bronchodilator Agents / therapeutic use*
  • Case-Control Studies
  • Drug Resistance / genetics
  • Female
  • Humans
  • India
  • Male
  • Middle Aged
  • Mutation, Missense
  • Polymorphism, Single Nucleotide*
  • Receptors, Adrenergic, beta-2 / genetics*

Substances

  • ADRB2 protein, human
  • Adrenergic beta-2 Receptor Agonists
  • Bronchodilator Agents
  • Receptors, Adrenergic, beta-2
  • Albuterol