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Influences of matrix metalloproteinase-3 gene variation on extent of coronary atherosclerosis and risk of myocardial infarction

Influences of matrix metalloproteinase-3 gene variation on extent of coronary atherosclerosis and risk of myocardial infarction
Influences of matrix metalloproteinase-3 gene variation on extent of coronary atherosclerosis and risk of myocardial infarction
Objectives The aim of this study was to assess matrix metallloproteinase-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.
apo, apolipoprotein, cad, coronary artery disease, bi-ddf, bi-directional dideoxy fingerprinting, mi, myocardial infarction, mmp, matrix metalloproteinase, pcr, polymerase chain reaction
0735-1097
2130-2137
Beyzade, Seyyare
1762a4db-4300-4ef0-9140-a9bada45ccc3
Zhang, Shaoli
731ca399-f117-4aff-8d1d-36e59c919539
Wong, Yuk-ki
a6099f58-6987-4584-a1a7-9ea618f4abb8
Day, Ian N.M.
b749b30a-1f4c-40eb-af0e-a50427388b39
Eriksson, Per
b7dab14d-9f76-41c7-b1d6-f2f564454fce
Ye, Shu
132b6474-1927-4f93-80db-2c620a31c1ab
Beyzade, Seyyare
1762a4db-4300-4ef0-9140-a9bada45ccc3
Zhang, Shaoli
731ca399-f117-4aff-8d1d-36e59c919539
Wong, Yuk-ki
a6099f58-6987-4584-a1a7-9ea618f4abb8
Day, Ian N.M.
b749b30a-1f4c-40eb-af0e-a50427388b39
Eriksson, Per
b7dab14d-9f76-41c7-b1d6-f2f564454fce
Ye, Shu
132b6474-1927-4f93-80db-2c620a31c1ab

Beyzade, Seyyare, Zhang, Shaoli, Wong, Yuk-ki, Day, Ian N.M., Eriksson, Per and Ye, Shu (2003) Influences of matrix metalloproteinase-3 gene variation on extent of coronary atherosclerosis and risk of myocardial infarction. Journal of the American College of Cardiology, 41 (12), 2130-2137. (doi:10.1016/S0735-1097(03)00482-0).

Record type: Article

Abstract

Objectives The aim of this study was to assess matrix metallloproteinase-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.

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More information

Published date: 2003
Additional Information: Clinical research: myocardial infarction
Keywords: apo, apolipoprotein, cad, coronary artery disease, bi-ddf, bi-directional dideoxy fingerprinting, mi, myocardial infarction, mmp, matrix metalloproteinase, pcr, polymerase chain reaction

Identifiers

Local EPrints ID: 24629
URI: https://eprints.soton.ac.uk/id/eprint/24629
ISSN: 0735-1097
PURE UUID: 0b0789d6-df24-4ebb-9dac-a8582801ecce

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Date deposited: 04 Apr 2006
Last modified: 15 Jul 2019 19:17

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