Genotypes in matrix metalloproteinase 9 are a risk factor for COPD

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Authors: Yohannes Tesfaigzi, Orrin B Myers, Christine A Stidley, Kurt Schwalm, Maria Picchi, et al

Published Date May 2006 Volume 2006:1(3) Pages 267 - 278

DOI: http://dx.doi.org/10.2147/COPD.S

Yohannes Tesfaigzi¹, Orrin B Myers², Christine A Stidley², Kurt Schwalm¹, Maria Picchi¹, Richard E Crowell³, Frank D Gilliland⁴, Steven A Belinsky¹

¹Lovelace Respiratory Research Institute, Albuquerque, NM, USA; ²Department of Internal Medicine, New Mexico Center for Environmental Health Sciences, University of New Mexico, Albuquerque, USA; ³Department of Internal Medicine, University of New Mexico, and Pulmonary Section, New Mexico VA Health Care System, Albuquerque, NM, USA; ⁴Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA

Abstract: A growing body of evidence indicates that matrix metalloproteinases (MMPs) play a role in the pathogenesis of COPD. Therefore, we conducted a candidate gene association study of 4 promoter polymorphisms that are known to modify expression levels of the MMP-1, MMP-2, and MMP-9 genes and a Gln279Arg polymorphism in exon 6 of MMP-9 that modifies the substrate-binding region. We examined the association of each variant and haplotypes in 385 male veterans with greater than 20 pack-years of cigarette smoking whose COPD status was characterized using spirometry. The association of these polymorphisms was also examined with decline of pulmonary function in a subset of participants. Only the 279Arg variant was more common in participants with COPD and the homozygous variant was associated with a 3-fold increased risk for COPD. In the haplotype analysis, the haplotype comprising the 249Arg and the CA promoter polymorphism within the MMP-9 gene was associated with risk, suggesting that either 279Arg or a linked variant on this haplotype underlies the association. No association of this polymorphism was found with decline in pulmonary function. These studies show that variants of the MMP-9 gene are associated with COPD in this cohort of veterans.

Keywords: metalloproteinase, smoking, pulmonary function, single nucleotide polymorphism, molecular epidemiology