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


CONCLUSIONS
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.
Jin
Ying
Y
Center for Health Services Research, Henry Ford Health System, Detroit, Mich; Wayne State University School of Medicine, Detroit, Mich 48202, USA.
Hu
Donglei
D
Peterson
Edward L
EL
Eng
Celeste
C
Levin
Albert M
AM
Wells
Karen
K
Beckman
Kenneth
K
Kumar
Rajesh
R
Seibold
Max A
MA
Karungi
Gloria
G
Zoratti
Amanda
A
Gaggin
John
J
Campbell
Janis
J
Galanter
Joshua
J
Chapela
Rocío
R
Rodríguez-Santana
José R
JR
Watson
H Geoffrey
HG
Meade
Kelley
K
Lenoir
Michael
M
Rodríguez-Cintrón
William
W
Avila
Pedro C
PC
Lanfear
David E
DE
Burchard
Esteban G
EG
Williams
L Keoki
LK
D000280:Administration, Inhalation; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D002648:Child; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D012129:Respiratory Function Tests; D016896:Treatment Outcome; D055815:Young Adult
D000305:Adrenal Cortex Hormones; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1