PMID- 12821236
OWN - NLM
STAT- MEDLINE
DCOM- 20030709
LR  - 20190708
IS  - 0735-1097 (Print)
IS  - 0735-1097 (Linking)
VI  - 41
IP  - 12
DP  - 2003 Jun 18
TI  - Influences of matrix metalloproteinase-3 gene variation on extent of coronary 
      atherosclerosis and risk of myocardial infarction.
PG  - 2130-7
AB  - OBJECTIVES: The aim of this study was to assess matrix metalloproteinase-3 (MMP3) 
      gene variation in relation to the degree of coronary atherosclerosis and risk of 
      myocardial infarction (MI) in patients with coronary artery disease. METHODS: In 
      this study, we systematically screened the promoter and coding regions for 
      sequence variants. All polymorphisms identified were analyzed in 1,240 
      individuals undergoing coronary angiography. Functional analyses of the 
      polymorphisms were carried out with the use of report assays and electrophoretic 
      mobility shift assays. RESULTS: Six novel polymorphisms were identified. The 
      6A/6A genotype was associated with greater number of coronary arteries with 
      significant stenosis (odds ratio [OR] 1.52, p = 0.008), whereas the 5A/5A and 
      5A/6A genotypes were associated with increased risk of MI (OR 2.02 and 1.78, p = 
      0.016 and 0.032, respectively). A stepwise logistic regression analysis with all 
      polymorphisms taken into account showed that the effect of MI susceptibility was 
      largely attributed to the 5A/6A polymorphism. In a stepwise logistic regression 
      analysis with all haplotypes as independent variables, the most common haplotype 
      (T-5A-A-A-G-A), and two rare haplotypes, all containing the 5A allele, were 
      associated with MI susceptibility. Functional studies showed that the 
      T-5A-A-A-G-A haplotype had a higher promoter activity in macrophages. 
      CONCLUSIONS: These data indicate that the effect of MMP3 gene variation is 
      attributable to the 5A/6A polymorphism and that individuals carrying the 6A/6A 
      genotype may be predisposed to developing atherosclerotic plaques with 
      significant stenosis, whereas those carrying the 5A allele may be predisposed to 
      developing unstable plaques.
FAU - Beyzade, Seyyare
AU  - Beyzade S
AD  - Human Genetics Division, Southampton University Medical School, Southampton, 
      United Kingdom.
FAU - Zhang, Shaoli
AU  - Zhang S
FAU - Wong, Yuk-ki
AU  - Wong YK
FAU - Day, Ian N M
AU  - Day IN
FAU - Eriksson, Per
AU  - Eriksson P
FAU - Ye, Shu
AU  - Ye S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Coll Cardiol
JT  - Journal of the American College of Cardiology
JID - 8301365
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Aged
MH  - Coronary Angiography
MH  - Coronary Artery Disease/*complications/diagnostic imaging/*genetics
MH  - Female
MH  - Genetic Variation/*genetics
MH  - Genotype
MH  - Humans
MH  - In Vitro Techniques
MH  - Male
MH  - Matrix Metalloproteinase 3/*genetics
MH  - Middle Aged
MH  - Myocardial Infarction/diagnostic imaging/*etiology/*genetics
MH  - Open Reading Frames/genetics
MH  - Polymorphism, Genetic/genetics
MH  - Promoter Regions, Genetic/genetics
MH  - Risk Assessment
MH  - Severity of Illness Index
EDAT- 2003/06/25 05:00
MHDA- 2003/07/10 05:00
CRDT- 2003/06/25 05:00
PHST- 2003/06/25 05:00 [pubmed]
PHST- 2003/07/10 05:00 [medline]
PHST- 2003/06/25 05:00 [entrez]
AID - S0735109703004820 [pii]
AID - 10.1016/s0735-1097(03)00482-0 [doi]
PST - ppublish
SO  - J Am Coll Cardiol. 2003 Jun 18;41(12):2130-7. doi: 10.1016/s0735-1097(03)00482-0.