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Genetic variants of microsomal epoxide hydrolase and glutamate-cysteine ligase in COPD

For affiliations, see Acknowledgements section.

CORRESPONDENCE: N. Kalsheker, Division of Clinical Chemistry, University Hospital, Nottingham, NG7 2UH, UK. Fax: 44 1158230722. E-mail: noor.kalsheker{at}nottingham.ac.uk

Keywords: Chronic obstructive pulmonary disease, genetic susceptibility, glutamate-cysteine ligase, microsomal epoxide hydrolase

Received: April 29, 2008
Accepted June 19, 2008

The genetic factors that contribute to the development of chronic obstructive pulmonary disease (COPD) are poorly understood. Many candidate genes have been proposed, including enzymes that protect the lung against oxidative stress, such as microsomal epoxide hydrolase (EPHX1) and glutamate-cysteine ligase (GCL). To date, most reported findings have been for EPHX1, particularly in relation to functional variants associated with fast and slow metabolism of epoxide intermediates. The present study aimed to identify any association of variation in these genes with COPD susceptibility or severity.

In total, 1,017 white COPD patients and 912 nondiseased age and sex matched smoking controls were genotyped for six single nucleotide polymorphisms (SNPs) in EPHX1 (including the fast and slow variants and associated haplotypes), and eight SNPs in the two genes encoding GCL. GCL is a rate-limiting enzyme in the synthesis of glutathione, a major contributor to anti-oxidant protection in the lung.

No association of variation was found in EPHX1 or GCL with susceptibility to COPD or disease severity.

This is the largest reported study to date and is well powered to detect associations that have been previously suggested. The current data indicate that these genetic variants are unlikely to be related to susceptibility or disease severity in white chronic obstructive pulmonary disease patients.

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