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Polymorphism of tandem repeat in promoter of 5-lipoxygenase in ASA-intolerant asthma: a positive association with airway hyperresponsiveness

  1. S.-H. Kim1,
  2. J.-S. Bae1,
  3. C.-H. Suh1,
  4. D.-H. Nahm1,
  5. J. W. Holloway2,
  6. H.-S. Park1

Article first published online: 6 MAY 2005

DOI: 10.1111/j.1398-9995.2005.00780.x

Issue

Allergy

Allergy

Volume 60, Issue 6, pages 760–765, June 2005

Additional Information

How to Cite

Kim, S.-H., Bae, J.-S., Suh, C.-H., Nahm, D.-H., Holloway, J. W. and Park, H.-S. (2005), Polymorphism of tandem repeat in promoter of 5-lipoxygenase in ASA-intolerant asthma: a positive association with airway hyperresponsiveness. Allergy, 60: 760–765. doi: 10.1111/j.1398-9995.2005.00780.x

Author Information

  1. 1

    Department of Allergy and Rheumatology, Ajou University School of Medicine, Suwon, Korea

  2. 2

    Human Genetics Division, University of Southampton School of Medicine, Southampton, UK

*H.-S. Park Department of Allergy and Rheumatology Ajou University School of Medicine Woncheondong San-5 Yongtonggu Suwon 442-749 Korea

Publication History

  1. Issue published online: 6 MAY 2005
  2. Article first published online: 6 MAY 2005
  3. Accepted for publication 1 October 2004

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Keywords:

  • 5-lipooxygenase;
  • 5-lipoxygenase-activating protein;
  • aspirin-intolerant asthma;
  • bronchial hyperresponsiveness;
  • tandem repeat polymorphism

Background:  5-Lipooxygenase (ALOX5) and 5-lipoxygenase-activating protein (ALOX5AP) are known as key enzymes in cysteinyl-leukotriene (cys-LT) production, critical mediators in aspirin acetylsalicyclic acid (ASA)-intolerant asthma (AIA). To date, studies of the promoter region of ALOX5 gene has revealed the potential influence of a variable number of tandem repeats of a Sp1- and Egr1-binding motif, on the transcription rate.

Methods:  To understand the pathological process that arises from cys-LT overproduction in AIA, we genotyped ALOX5 Sp1 and ALOX5AP poly(A) repeat promoter polymorphism by fluorescent-based capillary electrophoresis in the Korean population.

Results:  No significant differences in allele and genotype frequencies of the ALOX5 and ALOX5AP promoter polymorphisms were observed between the three groups. However, there was a strong association of the ALOX5 Sp1 repeat polymorphism with airway hyperresponsiveness (AHR; PC20 methacholine); AIA patients carrying a mutant allele (n > 5 or n < 5 repeats) showed increased AHR compared to AIA patients with wild-type genotype (P = 0.003).

Conclusion:  Although the alleles of the ALOX5 and ALOX5AP promoter cannot be considered as a prominent risk factor in the development of AIA, the genetic variant of tandem repeat (GGGCGG; Sp1-binding motif) in ALOX5 promoter is associated with the severity of airway hyperresponsiveness in AIA patients.

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