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Association Between Matrix Metalloproteinase Family Gene Polymorphisms and Ischemic Stroke: a Meta-analysis

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Abstract

Numerous studies have studied the relationships between matrix metalloproteinase (MMP) family gene polymorphisms and ischemic stroke. However, findings remain controversial. The objective of this study was to evaluate the relationships between MMP gene polymorphisms and ischemic stroke by using a meta-analysis. The PubMed, Embase, and Cochrane library databases were systemically searched. Data were extracted by two independent reviewers, and pooled odds ratio (OR) with 95 % confidence interval (CI) were calculated. Eleven studies were enrolled, including a total of 589 cases and 494 controls of MMP-1 -1607 1G/2G; 1,817 cases and 1,731 controls of MMP-3 -1612 5A/6A; and 540 cases and 547 controls of MMP-9 -1562C/T. Under the dominant and recessive models, respectively, the overall ORs and 95 % CIs of -1607 2G were 1.54, 1.16–2.04 (P = 0.005) and 1.25, 0.95–1.65 (P = 0.457); the overall ORs and 95 % CIs of -1612 6A were 1.01, 0.84–1.21 (P = 0.003) and 0.88, 0.75–1.03 (P = 0.057); and the overall ORs and 95 % CIs of -1562T were 0.78, 0.59–1.02 (P = 0.460) and 1.65, 0.73–3.75 (P = 0.340). No publication bias was found in this meta-analysis. This meta-analysis showed that MMP-1 -1607 1G/2G and MMP-3 -1612 5A/6A were risk factors for ischemic stroke, while MMP-9 -1562C/T was not associated with ischemic stroke.

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References

  1. Ghilardi G, Biondi ML, DeMonti M, Turri O, Guagnellini E, Scorza R (2002) Matrix metalloproteinase-1 and matrix metalloproteinase-3 gene promoter polymorphisms are associated with carotid artery stenosis. Stroke 33:2408–2412

    Article  CAS  PubMed  Google Scholar 

  2. Kalb R (2001) Spontaneous dissection of the carotid and vertebral arteries. N Engl J Med 345:467

    CAS  PubMed  Google Scholar 

  3. Brandt T, Orberk E, Weber R, Werner I, Busse O, Müller BT, Wigger F, Grau A, Grond-Ginsbach C, Hausser I (2001) Pathogenesis of cervical artery dissections: association with connective tissue abnormalities. Neurology 57:24–30

    Article  CAS  PubMed  Google Scholar 

  4. Lin RT, Chen CH, Tsai PC, Ho BL, Juo SH, Lin HF (2012) Sex-specific effect of matrix metalloproteinase-9 functional promoter polymorphism on carotid artery stiffness. Atherosclerosis 223:416–420

    Article  CAS  PubMed  Google Scholar 

  5. Koullias GJ, Ravichandran P, Korkolis DP, Rimm DL, Elefteriades JA (2004) Increased tissue microarray matrix metalloproteinase expression favors proteolysis in thoracic aortic aneurysms and dissections. Ann Thorac Surg 78:2106–2110

    Article  PubMed  Google Scholar 

  6. Jian Liu K, Rosenberg GA (2005) Matrix metalloproteinases and free radicals in cerebral ischemia. Free Radic Biol Med 39:71–80

    Article  CAS  PubMed  Google Scholar 

  7. Rosenberg GA, Sullivan N, Esiri MM (2001) White matter damage is associated with matrix metalloproteinases in vascular dementia. Stroke 32:1162–1168

    Article  CAS  PubMed  Google Scholar 

  8. Ye S (2006) Influence of matrix metalloproteinase genotype on cardiovascular disease susceptibility and outcome. Cardiovasc Res 69:636–645

    Article  CAS  PubMed  Google Scholar 

  9. Rundek T, Elkind MS, Pittman J, Boden-Albala B, Martin S, Humphries SE et al (2002) Carotid intima-media thickness is associated with allelic variants of stromelysin-1, interleukin-6, and hepatic lipase genes: the Northern Manhattan Prospective Cohort Study. Stroke 33:1420–1423

    Article  PubMed Central  PubMed  Google Scholar 

  10. Rauramaa R, Väisänen SB, Luong LA, Schmidt-Trücksäss A, Penttilä IM, Bouchard C, Töyry J, Humphries SE (2000) Stromelysin-1 and interleukin-6 gene promoter polymorphisms are determinants of asymptomatic carotid artery atherosclerosis. Arterioscler Thromb Vasc Biol 20:2657–2662

    Article  CAS  PubMed  Google Scholar 

  11. Abilleira S, Bevan S, Markus HS (2006) The role of genetic variants of matrix metalloproteinases in coronary and carotid atherosclerosis. J Med Genet 43:897–901

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Manolio TA, Boerwinkle E, O’Donnell CJ, Wilson AF (2004) Genetics of ultrasonographic carotid atherosclerosis. Arterioscler Thromb Vasc Biol 24:1567–1577

    Article  CAS  PubMed  Google Scholar 

  13. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560

    Article  PubMed Central  PubMed  Google Scholar 

  14. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Kaplan RC, Smith NL, Zucker S, Heckbert SR, Rice K, Psaty BM (2008) Matrix metalloproteinase-3 (MMP3) and MMP9 genes and risk of myocardial infarction, ischemic stroke, and hemorrhagic stroke. Atherosclerosis 201:130–137

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Ma AJ, Fan LY, Li WJ, Zhao HQ, Han Y, Jiang XS, Yi P, Li CL, Song S, Ma CL, Yao RY, Pan XD (2013) Association of matrix metalloproteinase-3 gene polymorphisms with subtypes of ischemic stroke. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 30:461–466

    CAS  PubMed  Google Scholar 

  17. Munshi A, Rajeshwar K, Kaul S, Al-Hazzani A, Alshatwi AA, Shafi G et al (2011) Association of tumor necrosis factor-α and matrix metalloproteinase-3 gene variants with stroke. Eur J Neurol 18:1053–1059

    Article  CAS  PubMed  Google Scholar 

  18. Huang X, Zhu M, Jin X, Zhang D, Wang L, Ye Z (2008) Association of matrix metalloproteinase-3 serum level and the promoter 5A/6A polymorphism of the MMP-3 gene with atherosclerotic cerebral infarction. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 25:653–656

    CAS  PubMed  Google Scholar 

  19. Djurić T, Stojković L, Zivković M, Končar I, Stanković A, Djordjević A et al (2012) Matrix metalloproteinase-1 promoter genotypes and haplotypes are associated with carotid plaque presence. Clin Biochem 45:1353–1356

    Article  PubMed  Google Scholar 

  20. Fu C, Xing Y, Song X (2011) The association of the metalloproteinase-3 gene promoter polymorphisms and the middle cerebral artery stenosis. Cell Biochem Biophys 59:185–189

    Article  CAS  PubMed  Google Scholar 

  21. Buss A, Pech K, Roelver S, Bloemeke B, Klotzsch C, Breuer S (2009) Functional polymorphisms in matrix metalloproteinases -1, -3, -9 and -12 in relation to cervical artery dissection. BMC Neurol 9:40

    Article  PubMed Central  PubMed  Google Scholar 

  22. Flex A, Gaetani E, Papaleo P, Straface G, Proia AS, Pecorini G et al (2004) Proinflammatory genetic profiles in subjects with history of ischemic stroke. Stroke 35:2270–2275

    Article  CAS  PubMed  Google Scholar 

  23. Wagner S, Kluge B, Koziol JA, Grau AJ, Grond-Ginsbach C (2004) MMP-9 polymorphisms are not associated with spontaneous cervical artery dissection. Stroke 35:e62–e64

    Article  CAS  PubMed  Google Scholar 

  24. Szczudlik P, Borratyńska A (2010) Association between the -1562C/T MMP-9 polymorphism and cerebrovascular disease in a Polish population. Neurol Neurochir Pol 44:350–357

    CAS  PubMed  Google Scholar 

  25. Djurić T, Zivković M, Radak D, Jekić D, Radak S, Stojković L et al (2008) Association of MMP-3 5A/6A gene polymorphism with susceptibility to carotid atherosclerosis. Clin Biochem 41:1326–1329

    Article  PubMed  Google Scholar 

  26. Pardo A, Selman M (2005) MMP-1: the elder of the family. Int J Biochem Cell Biol 37:283–288

    Article  CAS  PubMed  Google Scholar 

  27. Affara M, Dunmore BJ, Sanders DA, Johnson N, Print CG, Charnock-Jones DS (2011) MMP1 bimodal expression and differential response to inflammatory mediators is linked to promoter polymorphisms. BMC Genomics 12:43

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Ye S, Gale CR, Martyn CN (2003) Variation in the matrix metalloproteinase-1 gene and risk of coronary heart disease. Eur Heart J 24:1668–1671

    Article  CAS  PubMed  Google Scholar 

  29. Nikkari ST, O’Brien KD, Ferguson M, Hatsukami T, Welgus HG, Alpers CE et al (1995) Interstitial collagenase (MMP-1) expression in human carotid atherosclerosis. Circulation 92:1393–1398

    Article  CAS  PubMed  Google Scholar 

  30. Wu YW, Yang WS, Chen MF, Lee BC, Hung CS, Liu YC et al (2008) High serum level of matrix metalloproteinase-1 and its rapid surge after intervention in patients with significant carotid atherosclerosis. J Formos Med Assoc 107:93–98

    Article  CAS  PubMed  Google Scholar 

  31. Rutter JL, Mitchell TI, Butticè G, Meyers J, Gusella JF, Ozelius LJ et al (1998) A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter creates an Ets binding site and augments transcription. Cancer Res 58:5321–5325

    CAS  PubMed  Google Scholar 

  32. Galis ZS, Muszynski M, Sukhova GK, Simon-Morrissey E, Libby P (1995) Enhanced expression of vascular matrix metalloproteinases induced in vitro by cytokines and in regions of human atherosclerotic lesions. Ann N Y Acad Sci 748:501–507

    Article  CAS  PubMed  Google Scholar 

  33. Zhu C, Odeberg J, Hamsten A, Eriksson P (2006) Allele-specific MMP-3 transcription under in vivo conditions. Biochem Biophys Res Commun 348:1150–1156

    Article  CAS  PubMed  Google Scholar 

  34. Ye S, Eriksson P, Hamsten A, Kirkinen M, Humphries SE, Henney AM (1996) Progression of coronary atherosclerosis is associated with a common genetic variant of the human stromelysin-1 promoter which Results in reduced gene expression. J Biol Chem 271:13055–13060

    Article  CAS  PubMed  Google Scholar 

  35. Humphries SE, Luong LA, Talmud PJ, Frick MH, Kesaniemi YA, Pasternack A et al (1998) The 5A/6A polymorphism in the promoter of the stromelysin-1 (matrix metalloproteinase-3) gene predicts progression of angiographically determined coronary artery disease in men in the LOCAT gemfibrozil study: Lopid Coronary Angiography Trial. Atherosclerosis 139:49–56

    Article  CAS  PubMed  Google Scholar 

  36. Gnasso A, Motti C, Irace C, Carallo C, Liberatoscioli L, Bernardini S et al (2000) Genetic variation in human stromelysin gene promoter and common carotid geometry in healthy male subjects. Arterioscler Thromb Vasc Biol 20:1600–1605

    Article  CAS  PubMed  Google Scholar 

  37. Nagase H, Woessner JF Jr (1999) Matrix metalloproteinases. J Biol Chem 274:21491–21494

    Article  CAS  PubMed  Google Scholar 

  38. Zhang B, Ye S, Herrmann SM, Eriksson P, de Maat M, Evans A et al (1999) Functional polymorphism in the regulatory region of gelatinase B gene in relation to severity of coronary atherosclerosis. Circulation 99:1788–1794

    Article  CAS  PubMed  Google Scholar 

  39. Medley TL, Cole TJ, Dart AM, Gatzka CD, Kingwell BA (2004) Matrix metalloproteinase-9 genotype influences large artery stiffness through effects on aortic gene and protein expression. Arterioscler Thromb Vasc Biol 24:1479–1484

    Article  CAS  PubMed  Google Scholar 

  40. Blankenberg S, Rupprecht HJ, Poirier O, Bickel C, Smieja M, Hafner G et al (2003) Plasma concentrations and genetic variation of matrix metalloproteinase 9 and prognosis of patients with cardiovascular disease. Circulation 107:1579–1585

    Article  CAS  PubMed  Google Scholar 

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Sources of funding

The study was supported by grants from Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZY201302), Ministry of S&T Program of Chinese Arrhythmia Registration Study (2013BAI09B02), and the Ministry of S&T Program of Serious Arrhythmia based on Myocardial “intracellular logistics system” (No. 2013CB531105).

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The authors declare that they have no conflict of interest.

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Correspondence to Chang-Sheng Ma.

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Wen, D., Du, X., Nie, SP. et al. Association Between Matrix Metalloproteinase Family Gene Polymorphisms and Ischemic Stroke: a Meta-analysis. Mol Neurobiol 50, 979–985 (2014). https://doi.org/10.1007/s12035-014-8687-8

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  • DOI: https://doi.org/10.1007/s12035-014-8687-8

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