PMID- 21524282
OWN - NLM
STAT- MEDLINE
DCOM- 20110909
LR  - 20221207
IS  - 1465-993X (Electronic)
IS  - 1465-9921 (Print)
IS  - 1465-9921 (Linking)
VI  - 12
IP  - 1
DP  - 2011 Apr 27
TI  - Genetic variation in TIMP1 but not MMPs predict excess FEV1 decline in two 
      general population-based cohorts.
PG  - 57
LID - 10.1186/1465-9921-12-57 [doi]
AB  - BACKGROUND: 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 MMPs and TIMPs with respect to COPD development and lung function 
      decline in the general population are lacking. METHODS: We genotyped SNPs in MMP1 
      (G-1607GG), MMP2 (-1306 C/T), MMP9 (3 tagging SNPs), MMP12 (A-82G and Asn357Ser) 
      and TIMP1 (Phe124Phe and Ile158Ile) in 1390 Caucasians with multiple FEV1 
      measurements from a prospective cohort study in the general population. FEV1 
      decline was analyzed using linear mixed effect models adjusted for confounders. 
      Analyses of the X-chromosomal TIMP1 gene were stratified according to sex. All 
      significant associations were repeated in an independent general population 
      cohort (n=1152). RESULTS: MMP2 -1306 TT genotype carriers had excess FEV1 decline 
      (-4.0 ml/yr, p=0.03) compared to wild type carriers. TIMP1 Ile158Ile predicted 
      significant excess FEV1 decline in both males and females. TIMP1 Phe124Phe 
      predicted significant excess FEV1 decline in males only, which was replicated 
      (p=0.10) in the second cohort. The MMP2 and TIMP1 Ile158Ile associations were not 
      replicated. Although power was limited, we did not find associations with COPD 
      development. CONCLUSIONS: We for the first time show that TIMP1 Phe124Phe 
      contributes to excess FEV1 decline in two independent prospective cohorts, albeit 
      not quite reaching conventional statistical significance in the replication 
      cohort. SNPs in MMPs evidently do not contribute to FEV1 decline in the general 
      population.
FAU - van Diemen, C C
AU  - van Diemen CC
AD  - Department of Epidemiology, University of Groningen, Groningen, The Netherlands.
FAU - Postma, D S
AU  - Postma DS
FAU - Siedlinski, M
AU  - Siedlinski M
FAU - Blokstra, A
AU  - Blokstra A
FAU - Smit, H A
AU  - Smit HA
FAU - Boezen, H M
AU  - Boezen HM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110427
PL  - England
TA  - Respir Res
JT  - Respiratory research
JID - 101090633
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - EC 3.4.24.- (Matrix Metalloproteinases, Secreted)
RN  - EC 3.4.24.24 (MMP2 protein, human)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EC 3.4.24.65 (MMP12 protein, human)
RN  - EC 3.4.24.65 (Matrix Metalloproteinase 12)
RN  - EC 3.4.24.7 (MMP1 protein, human)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Analysis of Variance
MH  - Female
MH  - Forced Expiratory Volume/*genetics
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Linear Models
MH  - Lung/*physiopathology
MH  - Male
MH  - Matrix Metalloproteinase 1/genetics
MH  - Matrix Metalloproteinase 12/genetics
MH  - Matrix Metalloproteinase 2/genetics
MH  - Matrix Metalloproteinase 9/genetics
MH  - Matrix Metalloproteinases, Secreted/*genetics
MH  - Middle Aged
MH  - Netherlands
MH  - Phenotype
MH  - *Polymorphism, Single Nucleotide
MH  - Prospective Studies
MH  - Pulmonary Disease, Chronic Obstructive/enzymology/*genetics/physiopathology
MH  - Risk Assessment
MH  - Risk Factors
MH  - Tissue Inhibitor of Metalloproteinase-1/*genetics
MH  - White People/genetics
PMC - PMC3111362
EDAT- 2011/04/29 06:00
MHDA- 2011/09/10 06:00
PMCR- 2011/04/27
CRDT- 2011/04/29 06:00
PHST- 2010/12/17 00:00 [received]
PHST- 2011/04/27 00:00 [accepted]
PHST- 2011/04/29 06:00 [entrez]
PHST- 2011/04/29 06:00 [pubmed]
PHST- 2011/09/10 06:00 [medline]
PHST- 2011/04/27 00:00 [pmc-release]
AID - 1465-9921-12-57 [pii]
AID - 10.1186/1465-9921-12-57 [doi]
PST - epublish
SO  - Respir Res. 2011 Apr 27;12(1):57. doi: 10.1186/1465-9921-12-57.