association of mmp - 12 polymorphisms with severe and very severe copd a case control study of mmps - 1, 9 and 12 in a european population协会mmp - 12多态性与慢性阻塞性肺病严重和非常严重的病例对照研究基质金属蛋白酶- 9和12在欧洲人口.pdfVIP

Haq et al. BMC Medical Genetics 2010, 11:7 /1471-2350/11/7 RESEARCH ARTICLE Open Access Association of MMP - 12 polymorphisms with severe and very severe COPD: A case control study of MMPs - 1, 9 and 12 in a European population 1,2* 1 2 3 3 1 Imran Haq , Sally Chappell , Simon R Johnson , Juzer Lotya , Leslie Daly , Kevin Morgan , 1 4 4,8 5 6 7 Tamar Guetta-Baranes , Josep Roca , Roberto Rabinovich , Ann B Millar , Seamas C Donnelly , Vera Keatings , William MacNee8 9 9 10 11 6 , Jan Stolk , Pieter S Hiemstra , Massimo Miniati , Simonetta Monti , Clare M O’Connor , Noor Kalsheker1 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