ALOX5AP and LTA4H polymorphisms modify augmentation of bronchodilator responsiveness by leukotriene modifiers in Latinos.
BACKGROUND
Understanding the effects of interactions between multiple genes and asthma medications may aid in the understanding of the heterogeneous response to asthma therapies.


OBJECTIVE
To identify modulating effects of arachidonate 5-lipoxygenase-activating protein (ALOX5AP) and leukotriene A(4) hydrolase (LTA4H) gene polymorphisms on the drug-drug interaction between leukotriene modifiers and albuterol in Mexicans and Puerto Ricans.


METHODS
In a cross-sectional study of 293 Mexicans and 356 Puerto Ricans with asthma, ALOX5AP and LTA4H genes were sequenced, and interactions between gene polymorphisms and bronchodilator responsiveness to albuterol were compared between leukotriene modifier users and nonusers.


RESULTS
In heterozygotes and homozygotes for the minor allele at LTA4H single nucleotide polymorphism (SNP) rs2540491 and heterozygotes for the major allele at LTA4H SNP rs2540487, leukotriene modifier use was associated with a clinically significant increase in percent change in FEV(1) after albuterol administration of 7.10% (P = .002), 10.06% (P = .001), and 10.03% (P < .001), respectively. Presence of the major allele at ALOX5AP SNP rs10507391 or the minor allele at ALOX5AP SNP rs9551963 augmented this response. When stratified by ethnicity, these findings held true for Puerto Ricans but not Mexicans.


CONCLUSIONS
LTA4H and ALOX5AP gene polymorphisms modify the augmentation of bronchodilator responsiveness by leukotriene modifiers in Puerto Ricans but not Mexicans with asthma.
Tcheurekdjian
Haig
H
Allergy/Immunology Associates, Inc, and Case Western Reserve University, Cleveland, Ohio, USA. haig.tcheurekdjian@gmail.com
Via
Marc
M
De Giacomo
Anthony
A
Corvol
Harriet
H
Eng
Celeste
C
Thyne
Shannon
S
Chapela
Rocio
R
Rodriguez-Cintron
William
W
Rodriguez-Santana
Jose R
JR
Avila
Pedro C
PC
Burchard
Esteban González
EG
D058927:5-Lipoxygenase-Activating Proteins; D000293:Adolescent; D000420:Albuterol / Q000008:administration & dosage / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D003430:Cross-Sectional Studies; D004347:Drug Interactions; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D017058:Mexican Americans; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D055815:Young Adult
D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D001993:Bronchodilator Agents; D002352:Carrier Proteins; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D004851:Epoxide Hydrolases; D000420:Albuterol; C043134:leukotriene A4 hydrolase
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