The Journal of Allergy and Clinical Immunology
Volume 126, Issue 4 , Pages 853-858, October 2010

ALOX5AP and LTA4H polymorphisms modify augmentation of bronchodilator responsiveness by leukotriene modifiers in Latinos

  • Haig Tcheurekdjian, MD

      Affiliations

    • Allergy/Immunology Associates, Inc, and Case Western Reserve University, Cleveland, Ohio
    • These authors contributed equally to this work.
    • Corresponding Author InformationReprint requests: Haig Tcheurekdjian, MD, 1611 South Green Rd, #231, Cleveland, OH 44121.
    • ,
  • Marc Via, PhD

      Affiliations

    • Lung Biology Center, University of California, San Francisco, Calif
    • Institute for Human Genetics, University of California, San Francisco, Calif
    • These authors contributed equally to this work.
    • ,
  • Anthony De Giacomo, MS

      Affiliations

    • Lung Biology Center, University of California, San Francisco, Calif
    • ,
  • Harriet Corvol, MD

      Affiliations

    • Lung Biology Center, University of California, San Francisco, Calif
    • Department of Pediatric Pulmonary, UPMC/INSERM U893, Paris, France
    • ,
  • Celeste Eng, BS

      Affiliations

    • Lung Biology Center, University of California, San Francisco, Calif
    • ,
  • Shannon Thyne, MD

      Affiliations

    • Department of Pediatrics, University of California, San Francisco, Calif
    • ,
  • Rocio Chapela, MD

      Affiliations

    • Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico
    • ,
  • William Rodriguez-Cintron, MD

      Affiliations

    • Veterans Caribbean Health Care System, San Juan, Puerto Rico
    • ,
  • Jose R. Rodriguez-Santana, MD

      Affiliations

    • Centro de Neumologia Pediatrica, CSP, San Juan, Puerto Rico
    • ,
  • Pedro C. Avila, MD

      Affiliations

    • Division of Allergy-Immunology, Northwestern University, Chicago, Ill
    • ,
  • Esteban González Burchard, MD, MPH

      Affiliations

    • Allergy/Immunology Associates, Inc, and Case Western Reserve University, Cleveland, Ohio
    • Lung Biology Center, University of California, San Francisco, Calif
    • Institute for Human Genetics, University of California, San Francisco, Calif
    • Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, Calif
    • ,
  • Genetics of Asthma in Latino Americans Study

Received 24 February 2010; received in revised form 25 May 2010; accepted 28 June 2010. published online 01 September 2010.

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.

Key words: Asthma, leukotriene, leukotriene modifier, Latino, albuterol, drug responsiveness, association study, genetic polymorphism

Abbreviations used: ALOX5AP, Arachidonate 5-lipoxygenase-activating protein, BMI, Body mass index, %ΔFEV1, Percent change in FEV1, GALA, Genetics of Asthma in Latino Americans, LTA4H, Leukotriene A4 hydrolase, LTB4, Leukotriene B4, SNP, Single nucleotide polymorphism

 

 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.

 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.

PII: S0091-6749(10)01119-X

doi:10.1016/j.jaci.2010.06.048

The Journal of Allergy and Clinical Immunology
Volume 126, Issue 4 , Pages 853-858, October 2010

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