Respiratory Medicine
Volume 105, Issue 3 , Pages 506-510, March 2011

The cyclooxygenase-2-765C promoter polymorphism protects against the development of chronic obstructive pulmonary disease

This Paper is dedicated to our close friend and mentor Professor Peter Black who died suddenly in January 2010. Peter was instrumental in the conception and design of this study. His death is a huge loss to the COPD research community and to us personally.

  • Lian Wu

      Affiliations

    • Department of Pharmacology & Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand
    • Corresponding Author InformationCorresponding author. Tel.: +64 9 3737599x86023; fax: +64 9 3737556.
    • ,
  • Mervyn Merrilees

      Affiliations

    • Department of Anatomy with Radiology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand
    • ,
  • Robert P. Young

      Affiliations

    • Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand
    • ,
  • Peter N. Black

      Affiliations

    • Department of Pharmacology & Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand

Received 31 May 2010; accepted 3 August 2010. published online 19 August 2010.

Summary 

Background

Susceptibility to Chronic Obstructive Pulmonary Disease (COPD) has a genetic component. We undertook a study to determine if a genetic variant of the gene encoding the cyclooxygenase-2 gene influences the likelihood of developing COPD.

Methods

In a case control study the frequency of a single nucleotide polymorphism in the promoter region of the cyclooxygenase-2 gene (-765 G → C) was determined in 205 subjects with COPD, 171 chronic smokers with normal lung function (resistant smokers) and 95 healthy blood donors using the polymerase chain reaction and restriction enzyme fragment length polymorphism.

Results

The frequency of the C allele of the -765 cyclooxygenase-2 polymorphism was higher in resistant smokers (24.6%) compared with subjects with COPD (14.4%, OR = 1.98, 95% CI = 1.28–3.06, p = 0.003) and blood donors (14.7%, OR = 1.97, 95% CI = 1.14–3.41, p = 0.03).

Conclusions

The -765C allele, which has been shown to be associated with decreased promoter activity of the cyclooxygenase-2 gene, is more common in resistant smokers. This raises the possibility that decreased activity of cyclooxygenase-2 may protect smokers against the development of COPD.

Keywords: Cyclooxygenase-2, Genetic polymorphism, COPD, Smoking

Abbreviations: COPD, chronic obstructive pulmonary disease, -765 G→C, guanine to cytosine substitution at position -765 of the cyclooxygenase-2 gene, OR, odds ratio, PGE2, prostaglandin E2, MMP-2, matrix metalloproteinase-2, MMP-9, matrix metalloproteinase-9, FEV1, forced expiratory volume in 1 s, FVC, forced vital capacity, ATS, American Thoracic Society, PCR, polymerase chain reaction, RFLP, restriction enzyme fragment length polymorphism, DNA, deoxyribonucleic acid, SNP, single nucleotide polymorphism, TGF-β1, transforming growth factor beta 1, SD, standard deviation, SOD, superoxide dismutase

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PII: S0954-6111(10)00346-X

doi:10.1016/j.rmed.2010.08.002

Respiratory Medicine
Volume 105, Issue 3 , Pages 506-510, March 2011

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