title: Association of Beta 2 adrenergic receptor (Thr164Ile) polymorphism with Salbutamol refractoriness in severe asthmatics from Indian population.
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.
authors.affiliation: Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Hyderabad 500 016, India; National Institute of Pharmaceutical Education and Research, Hyderabad 500 037, India.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Bandaru
authors.affiliation: Government General and Chest Hospital, Gandhi Medical College and Osmania Medical College, Hyderabad 500 038, India.
authors.forename: Pramod
authors.initials: P
authors.lastname: Tarigopula
authors.affiliation: Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Hyderabad 500 016, India.
authors.forename: Jyothy
authors.initials: J
authors.lastname: Akka
authors.affiliation: Government General and Chest Hospital, Gandhi Medical College and Osmania Medical College, Hyderabad 500 038, India.
authors.forename: Vijaya Kumar
authors.initials: VK
authors.lastname: Marri
authors.affiliation: Government General and Chest Hospital, Gandhi Medical College and Osmania Medical College, Hyderabad 500 038, India.
authors.forename: Ramesh Kumar
authors.initials: RK
authors.lastname: Kattamuri
authors.affiliation: In silico Research Laboratory, Eminent Biosciences, Indore 452 010, India.
authors.forename: Anuraj
authors.initials: A
authors.lastname: Nayarisseri
authors.affiliation: Department of Genetics & Biotechnology, Osmania University, Hyderabad 500 007, India.
authors.forename: Madhavi
authors.initials: M
authors.lastname: Mangalarapu
authors.affiliation: Department of Genetics & Biotechnology, Osmania University, Hyderabad 500 007, India.
authors.forename: Swetha
authors.initials: S
authors.lastname: Vinukonda
authors.affiliation: Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Hyderabad 500 016, India.
authors.forename: Hema Prasad
authors.initials: HP
authors.lastname: Mundluru
authors.affiliation: Department of Genetics & Biotechnology, Osmania University, Hyderabad 500 007, India. Electronic address: drsomeswar@osmania.ac.in.
authors.forename: Someswar Rao
authors.initials: SR
authors.lastname: Sagurthi
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D000420:Albuterol / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy / Q000235:genetics*; D001993:Bronchodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016022:Case-Control Studies; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
chemical_list: C553443:ADRB2 protein, human; D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D018343:Receptors, Adrenergic, beta-2; D000420:Albuterol
keywords: Asthma severity; Bronchial asthma; Salbutamol refractoriness; Thr164Ile polymorphism