PMID- 22094117
OWN - NLM
STAT- MEDLINE
DCOM- 20120202
LR  - 20121003
IS  - 1097-6809 (Electronic)
IS  - 0741-5214 (Linking)
VI  - 55
IP  - 1
DP  - 2012 Jan
TI  - Polymorphisms of genes involved in extracellular matrix remodeling and abdominal 
      aortic aneurysm.
PG  - 171-179.e2
LID - 10.1016/j.jvs.2011.07.051 [doi]
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) has a multifactorial etiology and the 
      relevance of genetic factors is getting increasing interest, in particular those 
      related to the destructive remodeling of extracellular matrix. METHODS: We 
      performed a candidate gene association study of polymorphisms in genes coding 
      matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs), and elastin 
      (ELN) in AAA. DNA samples from 423 AAA patients and 423 controls were genotyped 
      for 12 polymorphisms in 10 genes: MMP1 (-1607G/GG), MMP2 (-735C/T; -1306C/T; 
      -1575 G/A), MMP3 (5A/6A), MMP9 (-1562C/T), MMP10 (A180G), MMP-12 (-82A/G), MMP-13 
      (-77A/G), TIMP1 (C434T), TIMP3 (-1296T/C), and ELN (G1355A). RESULTS: Genotype 
      distribution was significantly different between patients and controls for the 
      following polymorphisms: -1306C/T MMP2; 5A/6A MMP3; -77A/G MMP-13; G1355A ELN; 
      and C434T TIMP1. In a multivariable logistic regression analysis adjusted for 
      traditional cardiovascular risk factors and chronic obstructive pulmonary 
      disease, -1306C/T MMP2 (odds ratios [OR] = 0.55 [95% confidence interval, CI 
      .34-.85], P < .007) and G1355A ELN (OR = 0.64 ([95% CI .41-.99], P = .046) 
      polymorphisms resulted in independent protective factors for abdominal aortic 
      aneurysm (AAA), whereas 5A/6A MMP3 (OR = 1.82 [95% CI 1.04-3.12], P = .034) and 
      -77 A/G MMP-13 (OR = 2.14 [95% CI 1.18-3.86], P = .012) polymorphisms resulted in 
      independent risk factors for AAA. In a multivariable logistic regression analysis 
      adjusted for traditional cardiovascular factors and chronic obstructive pulmonary 
      disease, the prevalence of the contemporary presence of three or four genetic 
      risk conditions was a strong and independent determinant of AAA disease (OR = 
      2.96, 95% CI 1.67-5.24, P < .0001). For those polymorphisms independently 
      associated with AAA in this study (-1306C/T MMP2, 5A/6A MMP3, -77A/G MMP-13, and 
      G1355A ELN polymorphisms), we performed a meta-analysis of the available data 
      (this paper and literature data). We found a significant association with an 
      increased risk of AAA for MMP3 (AAA patients n = 1258, controls n = 1406: OR = 
      1.48 [95% CI = 1.23-1.78], I(2) = 0%) and MMP-13 (AAA patients n = 800, controls 
      n = 843: OR = 1.37 [95% CI = 1.04-1.82], I(2) = 25%) polymorphisms and a trend 
      that did not reach the statistical significance, toward a decreased risk of AAA 
      for MMP2 (AAA patients n = 1090, controls n = 1077: OR = 0.83 [95% CI = 
      .60-1.15], I(2) =7 1%) and ELN (AAA patients n = 904, controls n = 1069: OR = 
      0.79 [95% CI = .53-1.18], I(2) = 72%) polymorphisms. CONCLUSIONS: These findings 
      suggest that polymorphisms in MMP2, MMP3, MMP-13, and ELN genes may independently 
      contribute to the pathogenesis of AAA.
CI  - Copyright (c) 2012 Society for Vascular Surgery. Published by Mosby, Inc. All 
      rights reserved.
FAU - Saracini, Claudia
AU  - Saracini C
AD  - Department of Medical and Surgical Critical Care, University of Florence, 
      Atherothrombotic Diseases Center, Florence, Italy.
FAU - Bolli, Paola
AU  - Bolli P
FAU - Sticchi, Elena
AU  - Sticchi E
FAU - Pratesi, Giovanni
AU  - Pratesi G
FAU - Pulli, Raffaele
AU  - Pulli R
FAU - Sofi, Francesco
AU  - Sofi F
FAU - Pratesi, Carlo
AU  - Pratesi C
FAU - Gensini, Gian Franco
AU  - Gensini GF
FAU - Abbate, Rosanna
AU  - Abbate R
FAU - Giusti, Betti
AU  - Giusti B
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
DEP - 20111116
PL  - United States
TA  - J Vasc Surg
JT  - Journal of vascular surgery
JID - 8407742
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 9007-58-3 (Elastin)
RN  - EC 3.4.24.- (MMP13 protein, human)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.24 (MMP2 protein, human)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - Aortic Aneurysm, Abdominal/enzymology/*genetics
MH  - Case-Control Studies
MH  - Chi-Square Distribution
MH  - Elastin/*genetics/metabolism
MH  - Extracellular Matrix/*metabolism
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Italy
MH  - Logistic Models
MH  - Matrix Metalloproteinase 13/genetics
MH  - Matrix Metalloproteinase 2/genetics
MH  - Matrix Metalloproteinase 3/genetics
MH  - Matrix Metalloproteinases/*genetics/metabolism
MH  - Odds Ratio
MH  - Phenotype
MH  - *Polymorphism, Single Nucleotide
MH  - Risk Assessment
MH  - Risk Factors
MH  - Tissue Inhibitor of Metalloproteinases/*genetics/metabolism
EDAT- 2011/11/19 06:00
MHDA- 2012/02/03 06:00
CRDT- 2011/11/19 06:00
PHST- 2011/04/13 00:00 [received]
PHST- 2011/07/06 00:00 [revised]
PHST- 2011/07/08 00:00 [accepted]
PHST- 2011/11/19 06:00 [entrez]
PHST- 2011/11/19 06:00 [pubmed]
PHST- 2012/02/03 06:00 [medline]
AID - S0741-5214(11)01670-3 [pii]
AID - 10.1016/j.jvs.2011.07.051 [doi]
PST - ppublish
SO  - J Vasc Surg. 2012 Jan;55(1):171-179.e2. doi: 10.1016/j.jvs.2011.07.051. Epub 2011 
      Nov 16.