Alessandra Scaparrotta1, Marica Franzago1, Maria Loredana Marcovecchio2, Sabrina Di Pillo1, Francesco Chiarelli1, Angelika Mohn1, Liborio Stuppia3,4. 1. 1 Department of Medicine and Aging, School of Medicine and Health Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy. 2. 2 Department of Pediatrics, University of Cambridge, Cambridge, United Kingdom. 3. 3 Laboratory of Molecular Genetics, Department of Psychological, Health and Territorial Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy. 4. 4 Center for Aging Sciences and Translational Medicine (CESI-Met), "G, d'Annunzio" University of Chieti-Pescara, Chieti, Italy.
Abstract
Background: An interindividual variability in response to short-acting bronchodilator drugs (short-acting inhaled β2-agonists, SABA) exists and this is linked in part to genetic factors. The aim of this study was to verify the influence of single nucleotide polymorphisms (SNPs) of a previously studied gene (ADRB2) and of new candidate genes (THRB and ARG1) on the acute response to SABA in children with asthma. Methods: One hundred asthmatic children (mean age 9.6 ± 3.0 years, 77 boys) underwent allergological and lung function evaluations. Spirometry was performed before and after bronchodilation test (BD test). The ADRB2 region containing the Arg16Gly (rs1042713) and Gln27Glu (rs1042714) variants were amplified by polymerase chain reaction, whereas ARG1 rs2781659 (A>G) and THRB rs892940 (G>A) SNPs were genotyped by high-resolution melting (HRM) analysis. Results: Seventy-seven percent of children developed asthma in the first 6 years of life. Allergic sensitization was observed in 92% (total immunoglobulin G: 529.8 ± 477. kU/L). All patients exhibited respiratory allergy: 43% has multiple respiratory, 22% to single respiratory, and 27% multiple respiratory and food allergies. Fifty four percent children showed positive BD response (forced expiratory volume in 1 second [FEV1] > 12%). Presence of Arg/Gly or Gly/Gly genotypes in position 16 of ADRB2 was significantly associated to a worse BD response (post-BD FEV1: 108.68% ± 15.62% in Arg/Arg vs. 101.86% ± 14.03% in Arg/Gly or Gly/Gly patients, p = 0.02). No significant association was found between spirometric parameters before and after BD for the other three examined SNPs. Conclusion: The influence of genetic variability on responsiveness to drugs could become a key parameter to optimize a tailored therapy for young patients with asthma, especially if drug-resistance occurs.
Background: An interindividual variability in response to short-acting bronchodilator drugs (short-acting inhaled β2-agonists, SABA) exists and this is linked in part to genetic factors. The aim of this study was to verify the influence of single nucleotide polymorphisms (SNPs) of a previously studied gene (ADRB2) and of new candidate genes (THRB and ARG1) on the acute response to SABA in children with asthma. Methods: One hundred asthmatic children (mean age 9.6 ± 3.0 years, 77 boys) underwent allergological and lung function evaluations. Spirometry was performed before and after bronchodilation test (BD test). The ADRB2 region containing the Arg16Gly (rs1042713) and Gln27Glu (rs1042714) variants were amplified by polymerase chain reaction, whereas ARG1rs2781659 (A>G) and THRBrs892940 (G>A) SNPs were genotyped by high-resolution melting (HRM) analysis. Results: Seventy-seven percent of children developed asthma in the first 6 years of life. Allergic sensitization was observed in 92% (total immunoglobulin G: 529.8 ± 477. kU/L). All patients exhibited respiratory allergy: 43% has multiple respiratory, 22% to single respiratory, and 27% multiple respiratory and food allergies. Fifty four percent children showed positive BD response (forced expiratory volume in 1 second [FEV1] > 12%). Presence of Arg/Gly or Gly/Gly genotypes in position 16 of ADRB2 was significantly associated to a worse BD response (post-BD FEV1: 108.68% ± 15.62% in Arg/Arg vs. 101.86% ± 14.03% in Arg/Gly or Gly/Glypatients, p = 0.02). No significant association was found between spirometric parameters before and after BD for the other three examined SNPs. Conclusion: The influence of genetic variability on responsiveness to drugs could become a key parameter to optimize a tailored therapy for young patients with asthma, especially if drug-resistance occurs.
Authors: Marija Rowane; Ryan Shilian; Devi K Jhaveri; Haig H Tcheurekdjian; Theordore H Sher; Robert Hostoffer Journal: Allergy Rhinol (Providence) Date: 2019-11-19