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Open Access Research article

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

Asif S Tulah1, Stuart G Parker2, Miriam F Moffatt3, Andrew J Wardlaw4, Martin J Connolly5 and Ian Sayers1*

Author Affiliations

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

2 Sheffield Institute for Studies on Ageing, University of Sheffield, Barnsley Hospital NHSFT, Barnsley, UK

3 National Heart and Lung Institute, Imperial College London, London, UK

4 Institute for Lung Health and Department of Infection, Immunity and Inflammation, Glenfield Hospital, University of Leicester, Leicester, UK

5 Freemasons' Department of Geriatric Medicine, University of Auckland, Auckland

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BMC Medical Genetics 2011, 12:173  doi:10.1186/1471-2350-12-173

Published: 29 December 2011

Abstract

Background

We have previously shown evidence that polymorphisms within genes controlling leukotriene B4 (LTB4) production (ALOX5AP and LTA4H) are associated with asthma susceptibility in children. Evidence also suggests a potential role of LTB4 in COPD disease mechanisms including recruitment of neutrophils to the lung. The aim of the current study was to see if these SNPs and those spanning the receptor genes for LTB4 (LTB4R1 and LTB4R2) influence baseline lung function and COPD susceptibility/severity in smokers.

Methods

Eight ALOX5AP, six LTA4H and six LTB4R single nucleotide polymorphisms (SNPs) were genotyped in a UK Smoking Cohort (n = 992). Association with baseline lung function (FEV1 and FEV1/FVC ratio) was determined by linear regression. Logistic regression was used to compare smoking controls (n = 176) with spirometry-defined COPD cases (n = 599) and to more severe COPD cases (GOLD stage 3 and 4, n = 389).

Results

No association with ALOX5AP, LTA4H or LTB4R survived correction for multiple testing. However, we showed modest association with LTA4H rs1978331C (intron 11) with increased FEV1 (p = 0.029) and with increased FEV1/FVC ratio (p = 0.020).

Conclusions

These data suggest that polymorphisms spanning ALOX5AP, LTA4H and the LTB4R locus are not major determinants of baseline lung function in smokers, but provide tentative evidence for LTA4H rs1978331C (intron 11) in determining baseline FEV1 and FEV1/FVC ratio in Caucasian Smokers in addition to our previously identified role in asthma susceptibility.