Dual-specificity phosphatase 1 as a pharmacogenetic modifier of inhaled steroid response among asthmatic patients

Ying Jin; Donglei Hu; Edward L. Peterson; Celeste Eng; Albert M. Levin; Karen Wells; Kenneth Beckman; Rajesh Kumar; Max A. Seibold; Gloria Karungi; Amanda Zoratti; John Gaggin; Janis Campbell; Joshua Galanter; Rocío Chapela; José R. Rodríguez-Santana; H. Geoffrey Watson; Kelley Meade; Michael Lenoir; William Rodríguez-Cintrón; Pedro C. Avila; David E. Lanfear; Esteban G. Burchard; L. Keoki Williams

doi:10.1016/j.jaci.2010.06.007

Dual-specificity phosphatase 1 as a pharmacogenetic modifier of inhaled steroid response among asthmatic patients

Ying Jin, Donglei Hu, Edward L. Peterson, Celeste Eng, Albert M. Levin, Karen Wells, Kenneth Beckman, Rajesh Kumar, Max A. Seibold, Gloria Karungi, Amanda Zoratti, John Gaggin, Janis Campbell, Joshua Galanter, Rocío Chapela, José R. Rodríguez-Santana, H. Geoffrey Watson, Kelley Meade, Michael Lenoir, William Rodríguez-CintrónPedro C. Avila, David E. Lanfear, Esteban G. Burchard, L. Keoki Williams

Laboratory Medicine and Pathology

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

Background: Inhaled corticosteroids (ICSs) are considered first-line treatment for persistent asthma, yet there is significant variability in treatment response. Dual-specificity phosphatase 1 (DUSP1) appears to mediate the anti-inflammatory action of corticosteroids. Objective: We sought to determine whether variants in the DUSP1 gene are associated with clinical response to ICS treatment. Methods: Study participants with asthma were drawn from the following multiethnic cohorts: the Genetics of Asthma in Latino Americans (GALA) study; the Study of African Americans, Asthma, Genes & Environments (SAGE); and the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE). We screened GALA study participants for genetic variants that modified the relationship between ICS use and bronchodilator response. We then replicated our findings in SAGE and SAPPHIRE participants. In a group of SAPPHIRE participants treated with ICSs for 6 weeks, we examined whether a DUSP1 polymorphism was associated with changes in FEV₁ and self-reported asthma control. Results: The DUSP1 polymorphisms rs881152 and rs34507926 localized to different haplotype blocks and appeared to significantly modify the relationship between ICS use and bronchodilator response among GALA study participants. This interaction was also seen for rs881152 among SAPPHIRE but not SAGE participants. Among the group of SAPPHIRE participants prospectively treated with ICSs for 6 weeks, rs881152 genotype was significantly associated with changes in self-reported asthma control but not FEV₁. Conclusion: DUSP1 polymorphisms were associated with clinical response to ICS therapy and therefore might be useful in the future to identify asthmatic patients more likely to respond to this controller treatment.

Original language	English (US)
Pages (from-to)	618-625.e1-e2
Journal	Journal of Allergy and Clinical Immunology
Volume	126
Issue number	3
DOIs	https://doi.org/10.1016/j.jaci.2010.06.007
State	Published - Sep 2010

Bibliographical note

Funding Information:
Supported by grants from the American Asthma Foundation Strategic Program for Asthma Research, the National Institutes of Health ( AI079139, AI061774, HL079055, and DK064695 ), and the Fund for Henry Ford Hospital to L. K. W. and the National Institutes of Health ( HL078885, AI077439, HL088133, U01 GM61390, ES015794 ) and the Flight Attendant Medical Research Institute (FAMRI) to E. G. B.

Funding Information:
Disclosure of potential conflict of interest: E. L. Peterson has received research support from the National Institutes of Health . R. Kumar has received research support from the National Institutes of Health/National Heart, Lung, and Blood Institute . J. R. Rodriguez-Santana has received research support from GlaxoSmithKline . W. Rodríguez-Cintrón has received research support from the University of California at San Francisco and Sociedad de Investigacion Cientifica, Inc , and is a member of the Scientific Committee of the American College of Chest Physicians. P. C. Avila has received research support from Genentech/Roche . D. E. Lanfear has received research support from Episource and the National Institutes of Health .

Keywords

Asthma
DUSP1
corticosteroid responsiveness
dual-specificity phosphatase 1
inhaled corticosteroids

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access

10.1016/j.jaci.2010.06.007

OpenUrl availability

Full text

Cite this

Jin, Y., Hu, D., Peterson, E. L., Eng, C., Levin, A. M., Wells, K., Beckman, K., Kumar, R., Seibold, M. A., Karungi, G., Zoratti, A., Gaggin, J., Campbell, J., Galanter, J., Chapela, R., Rodríguez-Santana, J. R., Watson, H. G., Meade, K., Lenoir, M., ... Williams, L. K. (2010). Dual-specificity phosphatase 1 as a pharmacogenetic modifier of inhaled steroid response among asthmatic patients. Journal of Allergy and Clinical Immunology, 126(3), 618-625.e1-e2. https://doi.org/10.1016/j.jaci.2010.06.007

Jin, Y, Hu, D, Peterson, EL, Eng, C, Levin, AM, Wells, K, Beckman, K, Kumar, R, Seibold, MA, Karungi, G, Zoratti, A, Gaggin, J, Campbell, J, Galanter, J, Chapela, R, Rodríguez-Santana, JR, Watson, HG, Meade, K, Lenoir, M, Rodríguez-Cintrón, W, Avila, PC, Lanfear, DE, Burchard, EG & Williams, LK 2010, 'Dual-specificity phosphatase 1 as a pharmacogenetic modifier of inhaled steroid response among asthmatic patients', Journal of Allergy and Clinical Immunology, vol. 126, no. 3, pp. 618-625.e1-e2. https://doi.org/10.1016/j.jaci.2010.06.007

@article{9adc69980bbc4e99a7687422315800e5,

title = "Dual-specificity phosphatase 1 as a pharmacogenetic modifier of inhaled steroid response among asthmatic patients",

abstract = "Background: Inhaled corticosteroids (ICSs) are considered first-line treatment for persistent asthma, yet there is significant variability in treatment response. Dual-specificity phosphatase 1 (DUSP1) appears to mediate the anti-inflammatory action of corticosteroids. Objective: We sought to determine whether variants in the DUSP1 gene are associated with clinical response to ICS treatment. Methods: Study participants with asthma were drawn from the following multiethnic cohorts: the Genetics of Asthma in Latino Americans (GALA) study; the Study of African Americans, Asthma, Genes & Environments (SAGE); and the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE). We screened GALA study participants for genetic variants that modified the relationship between ICS use and bronchodilator response. We then replicated our findings in SAGE and SAPPHIRE participants. In a group of SAPPHIRE participants treated with ICSs for 6 weeks, we examined whether a DUSP1 polymorphism was associated with changes in FEV1 and self-reported asthma control. Results: The DUSP1 polymorphisms rs881152 and rs34507926 localized to different haplotype blocks and appeared to significantly modify the relationship between ICS use and bronchodilator response among GALA study participants. This interaction was also seen for rs881152 among SAPPHIRE but not SAGE participants. Among the group of SAPPHIRE participants prospectively treated with ICSs for 6 weeks, rs881152 genotype was significantly associated with changes in self-reported asthma control but not FEV1. Conclusion: DUSP1 polymorphisms were associated with clinical response to ICS therapy and therefore might be useful in the future to identify asthmatic patients more likely to respond to this controller treatment.",

keywords = "Asthma, DUSP1, corticosteroid responsiveness, dual-specificity phosphatase 1, inhaled corticosteroids",

author = "Ying Jin and Donglei Hu and Peterson, {Edward L.} and Celeste Eng and Levin, {Albert M.} and Karen Wells and Kenneth Beckman and Rajesh Kumar and Seibold, {Max A.} and Gloria Karungi and Amanda Zoratti and John Gaggin and Janis Campbell and Joshua Galanter and Roc{\'i}o Chapela and Rodr{\'i}guez-Santana, {Jos{\'e} R.} and Watson, {H. Geoffrey} and Kelley Meade and Michael Lenoir and William Rodr{\'i}guez-Cintr{\'o}n and Avila, {Pedro C.} and Lanfear, {David E.} and Burchard, {Esteban G.} and Williams, {L. Keoki}",

note = "Funding Information: Supported by grants from the American Asthma Foundation Strategic Program for Asthma Research, the National Institutes of Health ( AI079139, AI061774, HL079055, and DK064695 ), and the Fund for Henry Ford Hospital to L. K. W. and the National Institutes of Health ( HL078885, AI077439, HL088133, U01 GM61390, ES015794 ) and the Flight Attendant Medical Research Institute (FAMRI) to E. G. B. Funding Information: Disclosure of potential conflict of interest: E. L. Peterson has received research support from the National Institutes of Health . R. Kumar has received research support from the National Institutes of Health/National Heart, Lung, and Blood Institute . J. R. Rodriguez-Santana has received research support from GlaxoSmithKline . W. Rodr{\'i}guez-Cintr{\'o}n has received research support from the University of California at San Francisco and Sociedad de Investigacion Cientifica, Inc , and is a member of the Scientific Committee of the American College of Chest Physicians. P. C. Avila has received research support from Genentech/Roche . D. E. Lanfear has received research support from Episource and the National Institutes of Health . ",

year = "2010",

month = sep,

doi = "10.1016/j.jaci.2010.06.007",

language = "English (US)",

volume = "126",

pages = "618--625.e1--e2",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Mosby Inc.",

number = "3",

}

TY - JOUR

T1 - Dual-specificity phosphatase 1 as a pharmacogenetic modifier of inhaled steroid response among asthmatic patients

AU - Jin, Ying

AU - Hu, Donglei

AU - Peterson, Edward L.

AU - Eng, Celeste

AU - Levin, Albert M.

AU - Wells, Karen

AU - Beckman, Kenneth

AU - Kumar, Rajesh

AU - Seibold, Max A.

AU - Karungi, Gloria

AU - Zoratti, Amanda

AU - Gaggin, John

AU - Campbell, Janis

AU - Galanter, Joshua

AU - Chapela, Rocío

AU - Rodríguez-Santana, José R.

AU - Watson, H. Geoffrey

AU - Meade, Kelley

AU - Lenoir, Michael

AU - Rodríguez-Cintrón, William

AU - Avila, Pedro C.

AU - Lanfear, David E.

AU - Burchard, Esteban G.

AU - Williams, L. Keoki

N1 - Funding Information: Supported by grants from the American Asthma Foundation Strategic Program for Asthma Research, the National Institutes of Health ( AI079139, AI061774, HL079055, and DK064695 ), and the Fund for Henry Ford Hospital to L. K. W. and the National Institutes of Health ( HL078885, AI077439, HL088133, U01 GM61390, ES015794 ) and the Flight Attendant Medical Research Institute (FAMRI) to E. G. B. Funding Information: Disclosure of potential conflict of interest: E. L. Peterson has received research support from the National Institutes of Health . R. Kumar has received research support from the National Institutes of Health/National Heart, Lung, and Blood Institute . J. R. Rodriguez-Santana has received research support from GlaxoSmithKline . W. Rodríguez-Cintrón has received research support from the University of California at San Francisco and Sociedad de Investigacion Cientifica, Inc , and is a member of the Scientific Committee of the American College of Chest Physicians. P. C. Avila has received research support from Genentech/Roche . D. E. Lanfear has received research support from Episource and the National Institutes of Health .

PY - 2010/9

Y1 - 2010/9

N2 - Background: Inhaled corticosteroids (ICSs) are considered first-line treatment for persistent asthma, yet there is significant variability in treatment response. Dual-specificity phosphatase 1 (DUSP1) appears to mediate the anti-inflammatory action of corticosteroids. Objective: We sought to determine whether variants in the DUSP1 gene are associated with clinical response to ICS treatment. Methods: Study participants with asthma were drawn from the following multiethnic cohorts: the Genetics of Asthma in Latino Americans (GALA) study; the Study of African Americans, Asthma, Genes & Environments (SAGE); and the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE). We screened GALA study participants for genetic variants that modified the relationship between ICS use and bronchodilator response. We then replicated our findings in SAGE and SAPPHIRE participants. In a group of SAPPHIRE participants treated with ICSs for 6 weeks, we examined whether a DUSP1 polymorphism was associated with changes in FEV1 and self-reported asthma control. Results: The DUSP1 polymorphisms rs881152 and rs34507926 localized to different haplotype blocks and appeared to significantly modify the relationship between ICS use and bronchodilator response among GALA study participants. This interaction was also seen for rs881152 among SAPPHIRE but not SAGE participants. Among the group of SAPPHIRE participants prospectively treated with ICSs for 6 weeks, rs881152 genotype was significantly associated with changes in self-reported asthma control but not FEV1. Conclusion: DUSP1 polymorphisms were associated with clinical response to ICS therapy and therefore might be useful in the future to identify asthmatic patients more likely to respond to this controller treatment.

AB - Background: Inhaled corticosteroids (ICSs) are considered first-line treatment for persistent asthma, yet there is significant variability in treatment response. Dual-specificity phosphatase 1 (DUSP1) appears to mediate the anti-inflammatory action of corticosteroids. Objective: We sought to determine whether variants in the DUSP1 gene are associated with clinical response to ICS treatment. Methods: Study participants with asthma were drawn from the following multiethnic cohorts: the Genetics of Asthma in Latino Americans (GALA) study; the Study of African Americans, Asthma, Genes & Environments (SAGE); and the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE). We screened GALA study participants for genetic variants that modified the relationship between ICS use and bronchodilator response. We then replicated our findings in SAGE and SAPPHIRE participants. In a group of SAPPHIRE participants treated with ICSs for 6 weeks, we examined whether a DUSP1 polymorphism was associated with changes in FEV1 and self-reported asthma control. Results: The DUSP1 polymorphisms rs881152 and rs34507926 localized to different haplotype blocks and appeared to significantly modify the relationship between ICS use and bronchodilator response among GALA study participants. This interaction was also seen for rs881152 among SAPPHIRE but not SAGE participants. Among the group of SAPPHIRE participants prospectively treated with ICSs for 6 weeks, rs881152 genotype was significantly associated with changes in self-reported asthma control but not FEV1. Conclusion: DUSP1 polymorphisms were associated with clinical response to ICS therapy and therefore might be useful in the future to identify asthmatic patients more likely to respond to this controller treatment.

KW - Asthma

KW - DUSP1

KW - corticosteroid responsiveness

KW - dual-specificity phosphatase 1

KW - inhaled corticosteroids

UR - http://www.scopus.com/inward/record.url?scp=77956392834&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956392834&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2010.06.007

DO - 10.1016/j.jaci.2010.06.007

M3 - Article

C2 - 20673984

AN - SCOPUS:77956392834

SN - 0091-6749

VL - 126

SP - 618-625.e1-e2

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 3

ER -

Dual-specificity phosphatase 1 as a pharmacogenetic modifier of inhaled steroid response among asthmatic patients

Abstract

Bibliographical note

Keywords

UN SDGs

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this