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The role of ALOX5AP, LTA4H and LTB4R polymorphisms in determining baseline lung function and COPD susceptibility in

Asif S Tulah1, Stuart G Parker, Miriam F Moffatt

  • 1Division of Therapeutics and Molecular Medicine, Nottingham Respiratory Biomedical Research Unit, University of Nottingham, Queen's Medical Centre, Nottingham, UK.

BMC Medical Genetics
|December 31, 2011
PubMed

Insights

Genetic variations in leukotriene B4 (LTB4) pathway genes do not strongly predict COPD risk in smokers. However, a specific LTA4H variant may influence baseline lung function (FEV1 and FEV1/FVC ratio).

Area of Science:

  • Pulmonary Medicine
  • Genetics
  • Respiratory Diseases

Background:

  • Leukotriene B4 (LTB4) pathway gene polymorphisms (ALOX5AP, LTA4H) are linked to childhood asthma.
  • LTB4 may play a role in Chronic Obstructive Pulmonary Disease (COPD) by recruiting neutrophils to the lungs.

Purpose of the Study:

  • Investigate if single nucleotide polymorphisms (SNPs) in LTB4 production and receptor genes influence lung function and COPD risk in smokers.
  • Determine the association of LTB4 pathway SNPs with baseline lung function (FEV1, FEV1/FVC ratio) and COPD susceptibility/severity.

Main Methods:

  • Genotyped 8 ALOX5AP, 6 LTA4H, and 6 LTB4R SNPs in a UK Smoking Cohort (n=992).
  • Used linear regression for baseline lung function and logistic regression for COPD case-control and severity analyses.

Main Results:

  • No significant associations for ALOX5AP, LTA4H, or LTB4R SNPs remained after correction for multiple testing.
  • A modest association was observed for LTA4H rs1978331C (intron 11) with increased FEV1 (p=0.029) and FEV1/FVC ratio (p=0.020).

Conclusions:

  • LTB4 pathway gene polymorphisms are not major determinants of baseline lung function in smokers.
  • Tentative evidence suggests LTA4H rs1978331C influences baseline FEV1 and FEV1/FVC ratio in Caucasian smokers, in addition to its role in asthma susceptibility.
Abstract

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