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Joseph S. Coselli
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J Thorac Cardiovasc Surg 2006;131:1045-1052
© 2006 The American Association for Thoracic Surgery

Surgery for Acquired Cardiovascular Disease

A single nucleotide polymorphism in the matrix metalloproteinase 9 gene (–8202A/G) is associated with thoracic aortic aneurysms and thoracic aortic dissection

Li Chen, PhD a , Xinwen Wang, MD, PhD a , Stacey A. Carter, BA a , Ying H. Shen, MDPhD a , Heather R. Bartsch, MS a , Robert W. Thompson, MD b , Joseph S. Coselli, MD a , David L. Wilcken, MD c , Xing Li Wang, MD, PhD a , Scott A. LeMaire, MD a , *

a Cardiovascular Surgery Service, the Texas Heart Institute at St Luke's Episcopal Hospital, and the Division of Cardiothoracic Surgery, Baylor College of Medicine, Houston, Tex
b Departments of Surgery (Section of Vascular Surgery), Radiology, and Cell Biology and Physiology, Washington University School of Medicine, St Louis, Mo
c Cardiovascular Genetics Laboratory, Eastern Heart Clinic, Centre for Thrombosis and Vascular Research, University of New South Wales, Sydney, Australia

* Address for reprints: Scott A. LeMaire, MD, One Baylor Plaza, BCM 390, Houston, Texas 77030 (Email: slemaire{at}bcm.tmc.edu).

OBJECTIVE: Matrix metalloproteinase 9 plays an important role in the maintenance of the aortic extracellular matrix. Genetic variations that affect protease expression or activity might contribute to thoracic aortic disease. The purpose of this study was to determine whether 3 single nucleotide polymorphisms in the matrix metalloproteinase 9 gene are associated with thoracic aortic aneurysms and dissection.

METHODS: Genomic DNA was isolated from blood or aortic tissue from 28 patients with degenerative thoracic aortic aneurysms, 60 patients with thoracic aortic dissection, and 111 control patients. The frequency distributions of 3 matrix metalloproteinase 9 single nucleotide polymorphisms (–8202A/G, IVS4+3G/T, and 2003A/G [Q668R]) were determined by using genotyping accomplished with a real-time detection system. Associations between polymorphisms and disease were estimated with odds ratios and their 95% confidence intervals.

RESULTS: The frequency of the –8202G allele was significantly higher in patients with thoracic aortic aneurysms and aortic dissection (0.52 and 0.56, respectively) than in control subjects (0.36, P < .001). Patients with thoracic aortic aneurysms or dissection were nearly 5 times more likely than control subjects to have the G allele (adjusted odds ratio, 4.87; 95% confidence interval, 2.04–11.64). There were no significant associations between the IVS4+3G/T or 2003A/G polymorphisms and thoracic aortic disease.

CONCLUSIONS: The matrix metalloproteinase 9 –8202A/G polymorphism is associated with thoracic aortic aneurysms and dissection. Further studies are warranted to elucidate the functional role of the –8202A/G variant in matrix metalloproteinase 9 expression.

Abbreviations and Acronyms ECM = extracellular matrix; MMP = matrix metalloproteinase; OR = odds ratio; PCR = polymerase chain reaction; SNP = single nucleotide polymorphism; TAA = thoracic aortic aneurysm; TAD = thoracic aortic dissection




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