PMID- 17875574
OWN - NLM
STAT- MEDLINE
DCOM- 20080314
LR  - 20161124
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 16
IP  - 24
DP  - 2007 Dec 15
TI  - An increased frequency of the 5A allele in the promoter region of the MMP3 gene 
      is associated with abdominal aortic aneurysms.
PG  - 3002-7
AB  - Matrix metalloproteinase 3 (MMP3), is over expressed in the wall of abdominal 
      aortic aneurysms (AAA), while inactivation of the gene expressing this enzyme is 
      associated with reduced aneurysm formation in an experimental model. The 5A 
      allele of the 5A/6A polymorphism in the promoter region of the MMP3 gene is 
      associated with enhanced MMP3 expression. This study aimed to determine whether 
      the presence of the 5A allele in the MMP3 promoter is a risk factor for AAA, and 
      if this allele is associated with an increased expression of MMP3 in the aneurysm 
      wall. We compared the frequencies of the 5A and 6A alleles in AAA (n = 405), 
      aortic occlusive disease (AOD) (n = 123) and controls (n = 405). The 5A allele 
      frequency was higher in AAA compared with controls (odds ratio - OR 1.32, P = 
      0.005) and AOD (OR 1.684, P = 0.0004), but was similar in AOD compared to 
      controls (OR 0.78, P = 0.1). The ORs of the 5A/6A and the 5A/5A genotypes were 
      1.35 and 1.79, compared with 6A homozygotes. Although wall from 5A homozygotes 
      contained 17% more MMP3 mRNA than homozygotes (P = 0.049) the significance of 
      this was lost when adjusted for age and sex (P = 0.069), and size (P = 0.30). 
      Wall from 5A homozygotes did however contain over 45% more MMP3 protein than 
      heterozygotes (P = 0.009 when corrected for age and sex and P = 0.043 when 
      corrected for aneurysm size). It appears that an abnormality in the MMP3 gene is 
      part of the genetic profile that predisposes to aneurysmal disease.
FAU - Deguara, Jean
AU  - Deguara J
AD  - Academic Department of Surgery, Cardiovascular Division, King's College London, 
      St Thomas' Hospital London SE1 7EH, UK.
FAU - Burnand, Kevin G
AU  - Burnand KG
FAU - Berg, Jonathan
AU  - Berg J
FAU - Green, Peter
AU  - Green P
FAU - Lewis, Cathryn M
AU  - Lewis CM
FAU - Chinien, Ganesh
AU  - Chinien G
FAU - Waltham, Matthew
AU  - Waltham M
FAU - Taylor, Peter
AU  - Taylor P
FAU - Stern, Rowena F
AU  - Stern RF
FAU - Solomon, Ellen
AU  - Solomon E
FAU - Smith, Alberto
AU  - Smith A
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070917
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
EIN - Hum Mol Genet. 2009 Dec 1;18(23):4688. Stern, Rachel F [corrected to Stern, 
      Rowena F]
MH  - Aorta/diagnostic imaging
MH  - Aortic Aneurysm, Abdominal/diagnostic imaging/*genetics
MH  - Arterial Occlusive Diseases/diagnostic imaging/genetics
MH  - Cohort Studies
MH  - Female
MH  - *Gene Frequency
MH  - *Genetic Linkage
MH  - Heterozygote
MH  - Homozygote
MH  - Humans
MH  - Male
MH  - Matrix Metalloproteinase 3/*genetics
MH  - *Polymorphism, Single Nucleotide
MH  - *Promoter Regions, Genetic
MH  - Ultrasonography
EDAT- 2007/09/19 09:00
MHDA- 2008/03/15 09:00
CRDT- 2007/09/19 09:00
PHST- 2007/09/19 09:00 [pubmed]
PHST- 2008/03/15 09:00 [medline]
PHST- 2007/09/19 09:00 [entrez]
AID - ddm258 [pii]
AID - 10.1093/hmg/ddm258 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2007 Dec 15;16(24):3002-7. doi: 10.1093/hmg/ddm258. Epub 2007 Sep 
      17.