Genetic variation in <it>TIMP1 </it>but not <it>MMPs </it>predict excess FEV<sub>1 </sub>decline in two general population-based cohorts
<p>Abstract</p> <p>Background</p> <p>An imbalance in Matrix MetalloProteases (MMPs) and Tissue Inhibitors of MMPs (TIMPs) contributes to Chronic Obstructive Pulmonary Disease (COPD) development. Longitudinal studies investigating Single Nucleotide Polymorphisms (SNPs) i...
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doaj-21efd893698d46179ed5688c3c9aeef72020-11-24T21:35:39ZengBMCRespiratory Research1465-99212011-04-011215710.1186/1465-9921-12-57Genetic variation in <it>TIMP1 </it>but not <it>MMPs </it>predict excess FEV<sub>1 </sub>decline in two general population-based cohortsBlokstra ASiedlinski MPostma DSvan Diemen CCSmit HABoezen HM<p>Abstract</p> <p>Background</p> <p>An imbalance in Matrix MetalloProteases (MMPs) and Tissue Inhibitors of MMPs (TIMPs) contributes to Chronic Obstructive Pulmonary Disease (COPD) development. Longitudinal studies investigating Single Nucleotide Polymorphisms (SNPs) in <it>MMPs </it>and <it>TIMPs </it>with respect to COPD development and lung function decline in the general population are lacking.</p> <p>Methods</p> <p>We genotyped SNPs in <it>MMP1 </it>(G-1607GG), <it>MMP2 </it>(-1306 C/T), <it>MMP9 </it>(3 tagging SNPs), <it>MMP12 </it>(A-82G and Asn357Ser) and <it>TIMP1 </it>(Phe124Phe and Ile158Ile) in 1390 Caucasians with multiple FEV<sub>1 </sub>measurements from a prospective cohort study in the general population. FEV<sub>1 </sub>decline was analyzed using linear mixed effect models adjusted for confounders. Analyses of the X-chromosomal <it>TIMP1 </it>gene were stratified according to sex. All significant associations were repeated in an independent general population cohort (n = 1152).</p> <p>Results</p> <p><it>MMP2 </it>-1306 TT genotype carriers had excess FEV<sub>1 </sub>decline (-4.0 ml/yr, p = 0.03) compared to wild type carriers. <it>TIMP1 </it>Ile158Ile predicted significant excess FEV<sub>1 </sub>decline in both males and females. <it>TIMP1 </it>Phe124Phe predicted significant excess FEV<sub>1 </sub>decline in males only, which was replicated (p = 0.10) in the second cohort. The <it>MMP2 </it>and <it>TIMP1 </it>Ile158Ile associations were not replicated. Although power was limited, we did not find associations with COPD development.</p> <p>Conclusions</p> <p>We for the first time show that <it>TIMP1 </it>Phe124Phe contributes to excess FEV<sub>1 </sub>decline in two independent prospective cohorts, albeit not quite reaching conventional statistical significance in the replication cohort. SNPs in <it>MMPs </it>evidently do not contribute to FEV<sub>1 </sub>decline in the general population.</p> http://respiratory-research.com/content/12/1/57 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Blokstra A Siedlinski M Postma DS van Diemen CC Smit HA Boezen HM |
spellingShingle |
Blokstra A Siedlinski M Postma DS van Diemen CC Smit HA Boezen HM Genetic variation in <it>TIMP1 </it>but not <it>MMPs </it>predict excess FEV<sub>1 </sub>decline in two general population-based cohorts Respiratory Research |
author_facet |
Blokstra A Siedlinski M Postma DS van Diemen CC Smit HA Boezen HM |
author_sort |
Blokstra A |
title |
Genetic variation in <it>TIMP1 </it>but not <it>MMPs </it>predict excess FEV<sub>1 </sub>decline in two general population-based cohorts |
title_short |
Genetic variation in <it>TIMP1 </it>but not <it>MMPs </it>predict excess FEV<sub>1 </sub>decline in two general population-based cohorts |
title_full |
Genetic variation in <it>TIMP1 </it>but not <it>MMPs </it>predict excess FEV<sub>1 </sub>decline in two general population-based cohorts |
title_fullStr |
Genetic variation in <it>TIMP1 </it>but not <it>MMPs </it>predict excess FEV<sub>1 </sub>decline in two general population-based cohorts |
title_full_unstemmed |
Genetic variation in <it>TIMP1 </it>but not <it>MMPs </it>predict excess FEV<sub>1 </sub>decline in two general population-based cohorts |
title_sort |
genetic variation in <it>timp1 </it>but not <it>mmps </it>predict excess fev<sub>1 </sub>decline in two general population-based cohorts |
publisher |
BMC |
series |
Respiratory Research |
issn |
1465-9921 |
publishDate |
2011-04-01 |
description |
<p>Abstract</p> <p>Background</p> <p>An imbalance in Matrix MetalloProteases (MMPs) and Tissue Inhibitors of MMPs (TIMPs) contributes to Chronic Obstructive Pulmonary Disease (COPD) development. Longitudinal studies investigating Single Nucleotide Polymorphisms (SNPs) in <it>MMPs </it>and <it>TIMPs </it>with respect to COPD development and lung function decline in the general population are lacking.</p> <p>Methods</p> <p>We genotyped SNPs in <it>MMP1 </it>(G-1607GG), <it>MMP2 </it>(-1306 C/T), <it>MMP9 </it>(3 tagging SNPs), <it>MMP12 </it>(A-82G and Asn357Ser) and <it>TIMP1 </it>(Phe124Phe and Ile158Ile) in 1390 Caucasians with multiple FEV<sub>1 </sub>measurements from a prospective cohort study in the general population. FEV<sub>1 </sub>decline was analyzed using linear mixed effect models adjusted for confounders. Analyses of the X-chromosomal <it>TIMP1 </it>gene were stratified according to sex. All significant associations were repeated in an independent general population cohort (n = 1152).</p> <p>Results</p> <p><it>MMP2 </it>-1306 TT genotype carriers had excess FEV<sub>1 </sub>decline (-4.0 ml/yr, p = 0.03) compared to wild type carriers. <it>TIMP1 </it>Ile158Ile predicted significant excess FEV<sub>1 </sub>decline in both males and females. <it>TIMP1 </it>Phe124Phe predicted significant excess FEV<sub>1 </sub>decline in males only, which was replicated (p = 0.10) in the second cohort. The <it>MMP2 </it>and <it>TIMP1 </it>Ile158Ile associations were not replicated. Although power was limited, we did not find associations with COPD development.</p> <p>Conclusions</p> <p>We for the first time show that <it>TIMP1 </it>Phe124Phe contributes to excess FEV<sub>1 </sub>decline in two independent prospective cohorts, albeit not quite reaching conventional statistical significance in the replication cohort. SNPs in <it>MMPs </it>evidently do not contribute to FEV<sub>1 </sub>decline in the general population.</p> |
url |
http://respiratory-research.com/content/12/1/57 |
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