doi: 10.1161/hq1101.098229
© 2001 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Allele-Specific Regulation of Matrix Metalloproteinase-7 Promoter Activity Is Associated With Coronary Artery Luminal Dimensions Among Hypercholesterolemic Patients
From the Atherosclerosis Research Unit (S.J., C.W., A.H., P.E.), King Gustaf V Research Institute, Department of Medicine, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden, and the Department of Internal Medicine (D.H.W., A.M.Z.), University of Frankfurt, Frankfurt, Germany.
Correspondence to Dr Per Eriksson, King Gustaf V Research Institute, Karolinska Hospital, S-171 76 Stockholm, Sweden. E-mail Per.Eriksson{at}medks.ki.se
Abstract—— An enhanced expression of matrix metalloproteinase (MMP)-7 has previously been demonstrated in atherosclerotic and aneurysmal tissue. Because perturbed regulation of MMP-7 may influence the development of these diseases, we searched the MMP-7 promoter for functional polymorphisms. An A to G substitution at position -181 (-181 A/G) and a C to T substitution at position -153 (-153 C/T) with frequencies of 0.50 and 0.10, respectively, were identified. Allele-specific associations were studied in 350 patients undergoing percutaneous transluminal coronary angioplasty. Hypercholesterolemic patients carrying the -181G allele or the -153T allele had smaller reference luminal diameters before percutaneous transluminal coronary angioplasty. Reverse transcription–polymerase chain reaction demonstrated that expression of MMP-7 was confined to differentiated U937 cells. Northern blot analysis could not detect an effect of native or oxidatively modified low density lipoprotein on MMP-7 expression. Thus, the limitation of allele-specific effects on vessel wall remodeling to hypercholesterolemic patients may be secondary to lipid-mediated accumulation of MMP-7–expressing monocyte-derived macrophages within the vessel wall. Both polymorphisms influenced the binding of nuclear proteins. Furthermore, in transient transfection studies, the combination of the 2 rare alleles conferred an increased promoter activity. In conclusion, the present study identified and characterized 2 common polymorphisms in the promoter region of the MMP-7 gene that are functional in vitro and seem to influence coronary arterial dimensions in hypercholesterolemic patients with manifest coronary artery disease.
Key Words: matrix metalloproteinase-7 • matrilysin • polymorphisms • LDL • gene regulation
This article has been cited by other articles:
 |
|
 |
|
  W. Qiu, G. Zhou, Y. Zhai, X. Zhang, W. Xie, H. Zhang, H. Yang, L. Zhi, X. Yuan, X. Zhang, et al. No Association of MMP-7, MMP-8, and MMP-21 Polymorphisms with the Risk of Hepatocellular Carcinoma in a Chinese Population Cancer Epidemiol. Biomarkers Prev., September 1, 2008; 17(9): 2514 - 2518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Beeghly-Fadiel, J.-R. Long, Y.-T. Gao, C. Li, S. Qu, Q. Cai, Y. Zheng, Z.-X. Ruan, S. E. Levy, S. L. Deming, et al. Common MMP-7 Polymorphisms and Breast Cancer Susceptibility: A Multistage Study of Association and Functionality Cancer Res., August 1, 2008; 68(15): 6453 - 6459. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Borghese, J.-D. Chiche, D. Vernerey, C. Chenot, O. Mir, G. Bijaoui, C. Bonaiti-Pellie, and C. Chapron Genetic polymorphisms of matrix metalloproteinase 12 and 13 genes are implicated in endometriosis progression Hum. Reprod., May 1, 2008; 23(5): 1207 - 1213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. V. Cockle, N. Gopichandran, J. J. Walker, M. I. Levene, and N. M. Orsi Matrix Metalloproteinases and Their Tissue Inhibitors in Preterm Perinatal Complications Reproductive Sciences, October 1, 2007; 14(7): 629 - 645. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Abilleira, S. Bevan, and H. S Markus The role of genetic variants of matrix metalloproteinases in coronary and carotid atherosclerosis J. Med. Genet., December 1, 2006; 43(12): 897 - 901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sugimoto, S. Yoshida, S. Kennedy, M. Deguchi, N. Ohara, and T. Maruo Matrix Metalloproteinase-1 and -9 Promoter Polymorphisms and Endometrial Carcinoma Risk in a Japanese Population Reproductive Sciences, October 1, 2006; 13(7): 523 - 529. [Abstract] [PDF]
|
|
|
|
 |
|
 I. E. Milder, E. J. Feskens, I. C. Arts, H B. Bueno-de-Mesquita, P. C. Hollman, and D. Kromhout Intakes of 4 dietary lignans and cause-specific and all-cause mortality in the Zutphen Elderly Study. Am. J. Clinical Nutrition, August 1, 2006; 84(2): 400 - 405. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Zschenker, T. Illies, and D. Ameis Overexpression of lysosomal Acid lipase and other proteins in atherosclerosis. J. Biochem., July 1, 2006; 140(1): 23 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ye Influence of matrix metalloproteinase genotype on cardiovascular disease susceptibility and outcome Cardiovasc Res, February 15, 2006; 69(3): 636 - 645. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Shan, Z. Lian-Fu, D. Hui, G. Wei, W. Na, J. Xia, and L. Yan Polymorphisms in the promoter regions of the matrix metalloproteinases-7, -9 and the risk of endometriosis and adenomyosis in China Mol. Hum. Reprod., January 1, 2006; 12(1): 35 - 39. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhang, X. Jin, S. Fang, R. Wang, Y. Li, N. Wang, W. Guo, Y. Wang, D. Wen, L. Wei, et al. The functional polymorphism in the matrix metalloproteinase-7 promoter increases susceptibility to esophageal squamous cell carcinoma, gastric cardiac adenocarcinoma and non-small cell lung carcinoma Carcinogenesis, October 1, 2005; 26(10): 1748 - 1753. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Pont-Kingdon and E. Lyon Direct molecular haplotyping by melting curve analysis of hybridization probes: beta 2-adrenergic receptor haplotypes as an example Nucleic Acids Res., June 3, 2005; 33(10): e89 - e89. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Whatling, H. Bjork, S. Gredmark, A. Hamsten, and P. Eriksson Effect of macrophage differentiation and exposure to mildly oxidized LDL on the proteolytic repertoire of THP-1 monocytes J. Lipid Res., September 1, 2004; 45(9): 1768 - 1776. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Blons, S. Gad, F. Zinzindohoue, I. Maniere, J. Beauregard, D. Tregouet, D. Brasnu, P. Beaune, O. Laccourreye, and P. Laurent-Puig Matrix Metalloproteinase 3 Polymorphism: A Predictive Factor of Response to Neoadjuvant Chemotherapy in Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., April 15, 2004; 10(8): 2594 - 2599. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Ghilardi, M. L. Biondi, M. Erario, E. Guagnellini, and R. Scorza Colorectal Carcinoma Susceptibility and Metastases Are Associated with Matrix Metalloproteinase-7 Promoter Polymorphisms Clin. Chem., November 1, 2003; 49(11): 1940 - 1942. [Full Text] [PDF]
|
|
|
|
 |
|
 B. Burke, A. Giannoudis, K. P. Corke, D. Gill, M. Wells, L. Ziegler-Heitbrock, and C. E. Lewis Hypoxia-Induced Gene Expression in Human Macrophages: Implications for Ischemic Tissues and Hypoxia-Regulated Gene Therapy Am. J. Pathol., October 1, 2003; 163(4): 1233 - 1243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. B Jones, D. C Sane, and D. M Herrington Matrix metalloproteinases: A review of their structure and role in acute coronary syndrome Cardiovasc Res, October 1, 2003; 59(4): 812 - 823. [Abstract] [Full Text] [PDF]
|
|