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.

Association between beta 2 adrenergic receptor genetic polymorphisms and salbutamol responsiveness in asthmatic patients: a meta-analysis

“…We also conducted sensitivity analysis by removing the study deviating from HWE. No material changes of the pooled ORs were found after omitting any single study or the HWE-violating study [15] in all genetic models for Arg16Gly polymorphism and in dominant, heterozygous and additive models for Gln27Glu polymorphism. However, as for Gln27Glu polymorphism, the corresponding pooled ORs were considerably changed after deleting a single study [17] at a time in the recessive model (OR=0.348, 95% CI: 0.093-1.308, P =0.118), allele model (OR=0.700, 95% CI: 0.428-1.145, P =0.155) and homozygous model (OR=0.334, 95% CI: 0.087-1.288, P =0.111).…”

“…Figure 1 shows the flowchart of the study selection. Eight studies [13][14][15][16][17][18][19][20] focused on the ADRB2 Arg16Gly polymorphism involving 524 good responders and 370 poor responders to salbutamol. As for theADRB2 Gln27Glu polymorphism, five articles [13,16,17,19,20] were included with 171 good responders and 125 poor responders.…”

“…As for theADRB2 Gln27Glu polymorphism, five articles [13,16,17,19,20] were included with 171 good responders and 125 poor responders. Five studies [13,[15][16][17][18] included adult asthmatics, three studies [14,19,20] evaluated asthmatic children. Five studies [14-16, 18, 19] focused on Asian populations, and three studies [13,17,20] focused on Caucasian populations.…”

“…The quality evaluation was carried out using the Q-Genie tool. According to the criteria for studies without control group, seven articles [13][14][15][16][17][18][19] were of "good quality" and one [20] presented "moderate quality" (Table 1).…”

“…Several previous association studies have investigated the relationship between ADRB2 polymorphisms (Arg16Gly, Gln27Glu) and salbutamol responsiveness in asthmatic patients. However, the results are conflicting among different studies [13][14][15][16][17][18][19][20] .…”