ALOX5AP and LTA4H polymorphisms modify augmentation of bronchodilator responsiveness by leukotriene modifiers in Latinos - 07/08/11
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, Marc Via, PhD b, c, , Anthony De Giacomo, MS b, Harriet Corvol, MD b, f, Celeste Eng, BS b, Shannon Thyne, MD d, Rocio Chapela, MD g, William Rodriguez-Cintron, MD h, Jose R. Rodriguez-Santana, MD i, Pedro C. Avila, MD j, Esteban González Burchard, MD, MPH a, b, c, eGenetics of Asthma in Latino Americans Study
Reprint requests: Haig Tcheurekdjian, MD, 1611 South Green Rd, #231, Cleveland, OH 44121.Abstract |
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 A4 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 FEV1 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.
Conclusion |
LTA4H and ALOX5AP gene polymorphisms modify the augmentation of bronchodilator responsiveness by leukotriene modifiers in Puerto Ricans but not Mexicans with asthma.
El texto completo de este artículo está disponible en PDF.Key words : Asthma, leukotriene, leukotriene modifier, Latino, albuterol, drug responsiveness, association study, genetic polymorphism
Abbreviations used : ALOX5AP, BMI, %ΔFEV1, GALA, LTA4H, LTB4, SNP
Esquema
| Supported by the National Institutes of Health (HL078885, AI077439, HL088133), the Flight Attendant Medical Research Institute and RWJF Amos Medical Faculty Development Award to E.G.B., the Ernest S. Bazley Trust to P.C.A., the Beatriu de Pinos Postdoctoral Grant (2006 BP-A 10144) to M.V., and the Sandler Center for Basic Research in Asthma and the Sandler Family Supporting Foundation. |
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| Disclosure of potential conflict of interest: S. Thyne has received research support from the National Institutes of Health. The rest of the authors have declared that they have no conflict of interest. |
Vol 126 - N° 4
P. 853-858 - octobre 2010 Regresar al número
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