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Title: Association of MMP-2 polymorphisms with severe and very severe COPD: a case control study of MMPs-1, 9 and 12 in a European population.
Author: Haq, Imran
Chappell, Sally
Johnson, Simon R.
Lotya, Juzer
Daly, Leslie
Morgan, Kevin
Guetta-Baranes, Tamar
Roca Torrent, Josep
Rabinovich, Roberto Alejandro
Millar, Anna B.
Donnelly, Seamas C.
Keatings, Vera
MacNee, William
Stolk, Jan
Hiemstra, Pieter S.
Miniati, Massimo
Monti, Simonetta
O'Connor, Clare M.
Kalsheker, Noor
Keywords: Malalties pulmonars obstructives cròniques
Genètica molecular
Genètica mèdica
Chronic obstructive pulmonary diseases
Molecular genetics
Medical genetics
Issue Date: 15-Jan-2010
Publisher: BioMed Central
Abstract: BACKGROUND: Genetic factors play a role in chronic obstructive pulmonary disease (COPD) but are poorly understood. A number of candidate genes have been proposed on the basis of the pathogenesis of COPD. These include the matrix metalloproteinase (MMP) genes which play a role in tissue remodelling and fit in with the protease--antiprotease imbalance theory for the cause of COPD. Previous genetic studies of MMPs in COPD have had inadequate coverage of the genes, and have reported conflicting associations of both single nucleotide polymorphisms (SNPs) and SNP haplotypes, plausibly due to under-powered studies. METHODS: To address these issues we genotyped 26 SNPs, providing comprehensive coverage of reported SNP variation, in MMPs- 1, 9 and 12 from 977 COPD patients and 876 non-diseased smokers of European descent and evaluated their association with disease singly and in haplotype combinations. We used logistic regression to adjust for age, gender, centre and smoking history. RESULTS: Haplotypes of two SNPs in MMP-12 (rs652438 and rs2276109), showed an association with severe/very severe disease, corresponding to GOLD Stages III and IV. CONCLUSIONS: Those with the common A-A haplotype for these two SNPs were at greater risk of developing severe/very severe disease (p = 0.0039) while possession of the minor G variants at either SNP locus had a protective effect (adjusted odds ratio of 0.76; 95% CI 0.61 - 0.94). The A-A haplotype was also associated with significantly lower predicted FEV1 (42.62% versus 44.79%; p = 0.0129). This implicates haplotypes of MMP-12 as modifiers of disease severity.
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It is part of: BMC Medical Genomics, 2010, vol. 15, num. 11, p. 7
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ISSN: 1755-8794
Appears in Collections:Articles publicats en revistes (Medicina)

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