Publication

The Pharmacogenomics of Inhaled Corticosteroids and Lung Function Decline in COPD

Obeidat, M., Faiz, A., Li, X., van den Berge, M., Hansel, N. N., Joubert, P., Hao, K., Brandsma, C-A., Rafaels, N., Mathias, R., Ruczinski, I., Beaty, T. H., Barnes, K. C., Paul Man, S. F., Paré, P. D. & Sin, D. D., 1-Dec-2019, In : European Respiratory Journal. 54, 6, 12 p., 1900521.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Obeidat, M., Faiz, A., Li, X., van den Berge, M., Hansel, N. N., Joubert, P., Hao, K., Brandsma, C-A., Rafaels, N., Mathias, R., Ruczinski, I., Beaty, T. H., Barnes, K. C., Paul Man, S. F., Paré, P. D., & Sin, D. D. (2019). The Pharmacogenomics of Inhaled Corticosteroids and Lung Function Decline in COPD. European Respiratory Journal, 54(6), [1900521]. https://doi.org/10.1183/13993003.00521-2019

Author

Obeidat, Ma'en ; Faiz, Alen ; Li, Xuan ; van den Berge, Maarten ; Hansel, Nadia N ; Joubert, Philippe ; Hao, Ke ; Brandsma, Corry-Anke ; Rafaels, Nicholas ; Mathias, Rasika ; Ruczinski, Ingo ; Beaty, Terri H ; Barnes, Kathleen C ; Paul Man, S F ; Paré, Peter D ; Sin, Don D. / The Pharmacogenomics of Inhaled Corticosteroids and Lung Function Decline in COPD. In: European Respiratory Journal. 2019 ; Vol. 54, No. 6.

Harvard

Obeidat, M, Faiz, A, Li, X, van den Berge, M, Hansel, NN, Joubert, P, Hao, K, Brandsma, C-A, Rafaels, N, Mathias, R, Ruczinski, I, Beaty, TH, Barnes, KC, Paul Man, SF, Paré, PD & Sin, DD 2019, 'The Pharmacogenomics of Inhaled Corticosteroids and Lung Function Decline in COPD', European Respiratory Journal, vol. 54, no. 6, 1900521. https://doi.org/10.1183/13993003.00521-2019

Standard

The Pharmacogenomics of Inhaled Corticosteroids and Lung Function Decline in COPD. / Obeidat, Ma'en; Faiz, Alen; Li, Xuan; van den Berge, Maarten; Hansel, Nadia N; Joubert, Philippe; Hao, Ke; Brandsma, Corry-Anke; Rafaels, Nicholas; Mathias, Rasika; Ruczinski, Ingo; Beaty, Terri H; Barnes, Kathleen C; Paul Man, S F; Paré, Peter D; Sin, Don D.

In: European Respiratory Journal, Vol. 54, No. 6, 1900521, 01.12.2019.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Obeidat M, Faiz A, Li X, van den Berge M, Hansel NN, Joubert P et al. The Pharmacogenomics of Inhaled Corticosteroids and Lung Function Decline in COPD. European Respiratory Journal. 2019 Dec 1;54(6). 1900521. https://doi.org/10.1183/13993003.00521-2019


BibTeX

@article{241fb3cf9f34490a92fc7f54454f1634,
title = "The Pharmacogenomics of Inhaled Corticosteroids and Lung Function Decline in COPD",
abstract = "Inhaled corticosteroids (ICS) are widely prescribed for patients with chronic obstructive pulmonary disease (COPD), yet with variable outcomes and adverse reactions which may be genetically determined. The primary aim of the study was to identify the genetic determinants for FEV1 changes related to ICS therapy. In the Lung Health Study 2 (LHS-2), 1116 COPD patients were randomised to the ICS, triamcinolone acetonide (n=559), or placebo (n=557) with spirometry performed every 6 months for 3 years. We performed a pharmacogenomic genome-wide association study (GWAS) for the genotype-by-ICS treatment effect on 3 years of forced expiratory volume in 1 s (FEV1) changes (estimated as slope) in 802 genotyped LHS-2 participants. Replication was performed in 199 COPD patients randomised to the ICS, fluticasone or placebo. A total of five loci showed genotype-by-ICS interaction at p<5×10-6; of these, SNP rs111720447 on chromosome 7 was replicated (discovery p=4.8×10-6, replication p=5.9×10-5) with the same direction of interaction effect. ENCODE data revealed that in glucocorticoid treated (dexamethasone) A549 alveolar cell line, glucocorticoid receptor binding sites were located near SNP rs111720447. In stratified analyses of LHS-2, genotype at SNP rs111720447 was significantly associated with rate of FEV1 decline in patients taking ICS (C allele beta=56.35 mL·year-1, 95% confidence interval (CI)=29.96, 82.76 mL·yr-1) and also in patients who were assigned to placebo, though the relationship was weaker and in the opposite direction than that in the ICS group (C allele beta=-27.57 mL·year-1, 95% CI=-53.27, -1.87 mL·yr-1). The study uncovered genetic factors associated with FEV1 changes related to ICS in COPD patients, which may provide new insight on the potential biology of steroid responsiveness in COPD.",
author = "Ma'en Obeidat and Alen Faiz and Xuan Li and {van den Berge}, Maarten and Hansel, {Nadia N} and Philippe Joubert and Ke Hao and Corry-Anke Brandsma and Nicholas Rafaels and Rasika Mathias and Ingo Ruczinski and Beaty, {Terri H} and Barnes, {Kathleen C} and {Paul Man}, {S F} and Par{\'e}, {Peter D} and Sin, {Don D}",
note = "Copyright {\textcopyright}ERS 2019.",
year = "2019",
month = dec,
day = "1",
doi = "10.1183/13993003.00521-2019",
language = "English",
volume = "54",
journal = "European Respiratory Journal",
issn = "0903-1936",
publisher = "EUROPEAN RESPIRATORY SOC JOURNALS LTD",
number = "6",

}

RIS

TY - JOUR

T1 - The Pharmacogenomics of Inhaled Corticosteroids and Lung Function Decline in COPD

AU - Obeidat, Ma'en

AU - Faiz, Alen

AU - Li, Xuan

AU - van den Berge, Maarten

AU - Hansel, Nadia N

AU - Joubert, Philippe

AU - Hao, Ke

AU - Brandsma, Corry-Anke

AU - Rafaels, Nicholas

AU - Mathias, Rasika

AU - Ruczinski, Ingo

AU - Beaty, Terri H

AU - Barnes, Kathleen C

AU - Paul Man, S F

AU - Paré, Peter D

AU - Sin, Don D

N1 - Copyright ©ERS 2019.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Inhaled corticosteroids (ICS) are widely prescribed for patients with chronic obstructive pulmonary disease (COPD), yet with variable outcomes and adverse reactions which may be genetically determined. The primary aim of the study was to identify the genetic determinants for FEV1 changes related to ICS therapy. In the Lung Health Study 2 (LHS-2), 1116 COPD patients were randomised to the ICS, triamcinolone acetonide (n=559), or placebo (n=557) with spirometry performed every 6 months for 3 years. We performed a pharmacogenomic genome-wide association study (GWAS) for the genotype-by-ICS treatment effect on 3 years of forced expiratory volume in 1 s (FEV1) changes (estimated as slope) in 802 genotyped LHS-2 participants. Replication was performed in 199 COPD patients randomised to the ICS, fluticasone or placebo. A total of five loci showed genotype-by-ICS interaction at p<5×10-6; of these, SNP rs111720447 on chromosome 7 was replicated (discovery p=4.8×10-6, replication p=5.9×10-5) with the same direction of interaction effect. ENCODE data revealed that in glucocorticoid treated (dexamethasone) A549 alveolar cell line, glucocorticoid receptor binding sites were located near SNP rs111720447. In stratified analyses of LHS-2, genotype at SNP rs111720447 was significantly associated with rate of FEV1 decline in patients taking ICS (C allele beta=56.35 mL·year-1, 95% confidence interval (CI)=29.96, 82.76 mL·yr-1) and also in patients who were assigned to placebo, though the relationship was weaker and in the opposite direction than that in the ICS group (C allele beta=-27.57 mL·year-1, 95% CI=-53.27, -1.87 mL·yr-1). The study uncovered genetic factors associated with FEV1 changes related to ICS in COPD patients, which may provide new insight on the potential biology of steroid responsiveness in COPD.

AB - Inhaled corticosteroids (ICS) are widely prescribed for patients with chronic obstructive pulmonary disease (COPD), yet with variable outcomes and adverse reactions which may be genetically determined. The primary aim of the study was to identify the genetic determinants for FEV1 changes related to ICS therapy. In the Lung Health Study 2 (LHS-2), 1116 COPD patients were randomised to the ICS, triamcinolone acetonide (n=559), or placebo (n=557) with spirometry performed every 6 months for 3 years. We performed a pharmacogenomic genome-wide association study (GWAS) for the genotype-by-ICS treatment effect on 3 years of forced expiratory volume in 1 s (FEV1) changes (estimated as slope) in 802 genotyped LHS-2 participants. Replication was performed in 199 COPD patients randomised to the ICS, fluticasone or placebo. A total of five loci showed genotype-by-ICS interaction at p<5×10-6; of these, SNP rs111720447 on chromosome 7 was replicated (discovery p=4.8×10-6, replication p=5.9×10-5) with the same direction of interaction effect. ENCODE data revealed that in glucocorticoid treated (dexamethasone) A549 alveolar cell line, glucocorticoid receptor binding sites were located near SNP rs111720447. In stratified analyses of LHS-2, genotype at SNP rs111720447 was significantly associated with rate of FEV1 decline in patients taking ICS (C allele beta=56.35 mL·year-1, 95% confidence interval (CI)=29.96, 82.76 mL·yr-1) and also in patients who were assigned to placebo, though the relationship was weaker and in the opposite direction than that in the ICS group (C allele beta=-27.57 mL·year-1, 95% CI=-53.27, -1.87 mL·yr-1). The study uncovered genetic factors associated with FEV1 changes related to ICS in COPD patients, which may provide new insight on the potential biology of steroid responsiveness in COPD.

U2 - 10.1183/13993003.00521-2019

DO - 10.1183/13993003.00521-2019

M3 - Article

C2 - 31537701

VL - 54

JO - European Respiratory Journal

JF - European Respiratory Journal

SN - 0903-1936

IS - 6

M1 - 1900521

ER -

ID: 97446761