title: Analysis of ADRB2 (Arg16Gly) Gene Variant with Susceptibility, Pharmacogenetic Response and Disease Severity in South Indian Asthmatics.
abstract: β2-Adrenergic receptor (β2-AR) plays a crucial role in asthma pathophysiology by regulating, processes of the lung function, and clinical response to bronchodilators. The +46G>A- Gly16Arg polymorphism in the gene encoding β2 adrenergic receptor (ADRB2) has been associated with receptor non-responsiveness after β2-agonist exposure. In the present study, we sought to evaluate the possible association of Gly16Arg polymorphism with asthma susceptibility, pharmacogenetic response to Salbutamol, and varying degrees of disease severity. Three hundred ninety-eight clinically diagnosed patients and 456 healthy controls were enrolled for the study. Patients were classified into severity classes according to Global Initiative for Asthma guidelines. To assess bronchodilator response, spirometry was performed before and 15 min after Salbutamol (200 μg) delivery. Responders to Salbutamol were categorized if percentage reversibility was greater than or equal to 12% in them, while those showing reversibility less than 12% were classified as non-responders. Genotyping was carried out by ARMS-PCR technique. Statistical methods were applied to test for the significance of the results. In the present study, there was lack of significant association of polymorphism with disease susceptibility as well as with bronchodilator response. The polymorphism was not associated with mild and moderate asthma subtypes; however, there was a notable association with severe asthma subtype. In addition, the polymorphism was associated with severe asthma compared to subtypes of mild and moderate asthma combined. In a South Indian population, the ADRB2 Arg/Gly may not form a susceptible variant to develop asthma nor can be a standard predictive marker to bronchodilator response; nevertheless, the patterns in asthma severity can be predicted by analyzing this variant.
authors.affiliation: National Institute of Pharmaceutical Education and Research, Hyderabad, 500 037, India. srinivasgen08@gmail.com.|Department of Toxicology, Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Hyderabad, 500 016, India. srinivasgen08@gmail.com.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Bandaru
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: National Institute of Pharmaceutical Education and Research, Hyderabad, 500 037, India.
authors.forename: Mallika
authors.initials: M
authors.lastname: Alvala
authors.affiliation: Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Hyderabad, 500 016, India.
authors.forename: Deepika
authors.initials: D
authors.lastname: Ponnala
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
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D001993:Bronchodilator Agents / Q000008:administration & dosage; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000235:genetics*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: C553443:ADRB2 protein, human; D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D018343:Receptors, Adrenergic, beta-2; D000420:Albuterol
keywords: Arg16Gly variant; Salbutamol response; asthma severity; asthma susceptibility; bronchial asthma