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Haplotype effect of the matrix metalloproteinase-1 gene on risk of myocardial infarction.
Circ Res. 2005 Nov 11; 97(10):1070-6.CircR

Abstract

Myocardial infarction (MI) is commonly caused by atherosclerotic plaque rupture following excessive degradation of collagen fibers in the atherosclerotic lesion. We investigated whether interindividual variability in risk of MI was related to polymorphisms in the gene encoding matrix metalloproteinase (MMP)-1, a key fibrillar collagen-degrading enzyme. Several single nucleotide polymorphisms in the MMP1 gene promoter were identified following sequencing DNA samples from 30 individuals. An analysis of the polymorphisms in a cohort of British whites with coronary atherosclerosis, including 639 patients with MI and 538 non-MI subjects, revealed a haplotype effect of the -519A>G and -340T>C polymorphisms on risk of MI, with the A(-519)-C(-340) and G(-519)-T(-340) haplotypes being protective (odds ratio=0.70 [0.57 to 0.86]; P=0.0007), whereas the G(-519)-C(-340) haplotype increased MI risk (odds ratio=1.94 [1.15 to 3.28]; P=0.013). This finding was replicated in a subsequent analysis of 387 Swedish MI patients and 387 healthy controls (odds ratio=0.70 [0.55 to 0.89], P=0.003, for A(-519)-C(-340) and G(-519)-T(-340); odds ratio=1.54 [0.97 to 2.46], P=0.07, for G(-519)-C(-340)). In vitro assays showed that compared with the A(-519)-T(-340) haplotype, the A(-519)-C(-340) and G(-519)-T(-340) haplotypes had lower promoter activity, whereas the G(-519)-C(-340) haplotype had greater promoter strength, in driving gene expression in human macrophages. Haplotype-specific differences in MMP1 mRNA level in atherosclerotic tissues were also detected. The data indicate that MMP1 gene variation is a genetic factor contributing to interindividual differences in MI risk.

Authors+Show Affiliations

Human Genetics Division, School of Medicine, University of Southampton, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16210545

Citation

Pearce, Eve, et al. "Haplotype Effect of the Matrix Metalloproteinase-1 Gene On Risk of Myocardial Infarction." Circulation Research, vol. 97, no. 10, 2005, pp. 1070-6.
Pearce E, Tregouet DA, Samnegård A, et al. Haplotype effect of the matrix metalloproteinase-1 gene on risk of myocardial infarction. Circ Res. 2005;97(10):1070-6.
Pearce, E., Tregouet, D. A., Samnegård, A., Morgan, A. R., Cox, C., Hamsten, A., Eriksson, P., & Ye, S. (2005). Haplotype effect of the matrix metalloproteinase-1 gene on risk of myocardial infarction. Circulation Research, 97(10), 1070-6.
Pearce E, et al. Haplotype Effect of the Matrix Metalloproteinase-1 Gene On Risk of Myocardial Infarction. Circ Res. 2005 Nov 11;97(10):1070-6. PubMed PMID: 16210545.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Haplotype effect of the matrix metalloproteinase-1 gene on risk of myocardial infarction. AU - Pearce,Eve, AU - Tregouet,David-Alexandre, AU - Samnegård,Ann, AU - Morgan,Angharad R, AU - Cox,Charles, AU - Hamsten,Anders, AU - Eriksson,Per, AU - Ye,Shu, Y1 - 2005/10/06/ PY - 2005/10/8/pubmed PY - 2005/12/13/medline PY - 2005/10/8/entrez SP - 1070 EP - 6 JF - Circulation research JO - Circ Res VL - 97 IS - 10 N2 - Myocardial infarction (MI) is commonly caused by atherosclerotic plaque rupture following excessive degradation of collagen fibers in the atherosclerotic lesion. We investigated whether interindividual variability in risk of MI was related to polymorphisms in the gene encoding matrix metalloproteinase (MMP)-1, a key fibrillar collagen-degrading enzyme. Several single nucleotide polymorphisms in the MMP1 gene promoter were identified following sequencing DNA samples from 30 individuals. An analysis of the polymorphisms in a cohort of British whites with coronary atherosclerosis, including 639 patients with MI and 538 non-MI subjects, revealed a haplotype effect of the -519A>G and -340T>C polymorphisms on risk of MI, with the A(-519)-C(-340) and G(-519)-T(-340) haplotypes being protective (odds ratio=0.70 [0.57 to 0.86]; P=0.0007), whereas the G(-519)-C(-340) haplotype increased MI risk (odds ratio=1.94 [1.15 to 3.28]; P=0.013). This finding was replicated in a subsequent analysis of 387 Swedish MI patients and 387 healthy controls (odds ratio=0.70 [0.55 to 0.89], P=0.003, for A(-519)-C(-340) and G(-519)-T(-340); odds ratio=1.54 [0.97 to 2.46], P=0.07, for G(-519)-C(-340)). In vitro assays showed that compared with the A(-519)-T(-340) haplotype, the A(-519)-C(-340) and G(-519)-T(-340) haplotypes had lower promoter activity, whereas the G(-519)-C(-340) haplotype had greater promoter strength, in driving gene expression in human macrophages. Haplotype-specific differences in MMP1 mRNA level in atherosclerotic tissues were also detected. The data indicate that MMP1 gene variation is a genetic factor contributing to interindividual differences in MI risk. SN - 1524-4571 UR - https://www.unboundmedicine.com/medline/citation/16210545/Haplotype_effect_of_the_matrix_metalloproteinase_1_gene_on_risk_of_myocardial_infarction_ L2 - https://www.ahajournals.org/doi/10.1161/01.RES.0000189302.03303.11?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -