MMP12, Lung Function, and COPD in High-Risk Populations
| Autor: | Magnus Wickman, Inger Kull, Dawn L. DeMeo, Manuel E. Soto-Quiros, Edwin K. Silverman, Chris Stidley, Gary M. Hunninghake, Scott T. Weiss, Magnus Svartengren, Juan C. Celedón, Steven D. Shapiro, Christoph Lange, David Sparrow, Yohannes Tesfaigzi, Augusto A. Litonjua, Cilla Söderhäll, Craig P. Hersh, Erik Melén, Lydiana Avila, Göran Pershagen, Jessica Lasky-Su, Jenny Hallberg, Michael H. Cho, Juha Kere, Barbara J. Klanderman, Benjamin A. Raby |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Adult
Genetic Markers Male Pathology medicine.medical_specialty Population Single-nucleotide polymorphism Polymorphism Single Nucleotide Article Cohort Studies Pulmonary Disease Chronic Obstructive Forced Expiratory Volume Matrix Metalloproteinase 12 Internal medicine Humans Medicine Genetic Predisposition to Disease Child Promoter Regions Genetic education Alleles Aged Asthma education.field_of_study COPD business.industry Smoking Respiratory disease General Medicine Middle Aged medicine.disease respiratory tract diseases Minor allele frequency Cohort Female business Cohort study |
| Popis: | Genetic variants influencing lung function in children and adults may ultimately lead to the development of chronic obstructive pulmonary disease (COPD), particularly in high-risk groups.We tested for an association between single-nucleotide polymorphisms (SNPs) in the gene encoding matrix metalloproteinase 12 (MMP12) and a measure of lung function (prebronchodilator forced expiratory volume in 1 second [FEV(1)]) in more than 8300 subjects in seven cohorts that included children and adults. Within the Normative Aging Study (NAS), a cohort of initially healthy adult men, we tested for an association between SNPs that were associated with FEV(1) and the time to the onset of COPD. We then examined the relationship between MMP12 SNPs and COPD in two cohorts of adults with COPD or at risk for COPD.The minor allele (G) of a functional variant in the promoter region of MMP12 (rs2276109 [-82A--G]) was positively associated with FEV(1) in a combined analysis of children with asthma and adult former and current smokers in all cohorts (P=2x10(-6)). This allele was also associated with a reduced risk of the onset of COPD in the NAS cohort (hazard ratio, 0.65; 95% confidence interval [CI], 0.46 to 0.92; P=0.02) and with a reduced risk of COPD in a cohort of smokers (odds ratio, 0.63; 95% CI, 0.45 to 0.88; P=0.005) and among participants in a family-based study of early-onset COPD (P=0.006).The minor allele of a SNP in MMP12 (rs2276109) is associated with a positive effect on lung function in children with asthma and in adults who smoke. This allele is also associated with a reduced risk of COPD in adult smokers. |
| Databáze: | OpenAIRE |
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