Skip to main content

Advertisement

SpringerLink
Log in

Association between the MMP-9−1562 C>T polymorphism and the risk of stroke: a meta-analysis

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Matrix metalloproteinase (MMP)-9 so far is identified as extremely large and complicated MMP family member. Recently, dozens of studies have explored the association between a promoter polymorphism (−1562 C>T) in MMP-9 and stroke susceptibility. However, the conclusions of these studies still remain equivocal. Therefore, our current meta-analysis was conducted to investigate whether or not the MMP-9 promoter polymorphism is related to the risk of stroke. Electronic databases (PubMed, EMBASE, Web of Science, Cochrane Library and the Chinese Biomedical Literature Database) were searched to obtain all the available studies investigating this polymorphism and stroke from inception to October 2013. Overall and subgroup analyses were rigorously conducted after data extraction. Pooled odds ratio (OR) corresponding to 95 % confidence interval (CI) were estimated. The statistical analysis was performed using Review Manager 5.2. Totally, seven studies involving 1,624 cases and 1,525 controls were identified. The overall results suggested that there was no association of the C−1562T variant on stroke risk under the T allele versus C allele [OR T vs. C 0.98, 95 % CI (0.84, 1.15), P = 0.84], the dominant model [OR TT+TC vs. CC 0.95, 95 % CI (0.81, 1.13), P = 0.59], the recessive model [OR TT vs. TC+CC 1.55, 95 % CI (0.86, 2.81), P = 0.15], the homozygote comparison [OR TT vs. CC 1.48, 95 % CI (0.82, 2.68), P = 0.20] and the heterozygote comparison [OR TC vs. CC 0.93, 95 % CI (0.78, 1.10), P = 0.38]. In the subgroup analyses by ethnicity, age, stroke type and source of controls, no significant relations were observed in any genetic models. Our results indicated that MMP-9−1562 C>T polymorphism was not a risk factor for stroke. Further studies should focus on gene–gene and gene–environment interactions, and provide a more convincing explanation for this association.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Truelsen T, Heuschmann PU, Bonita R, Arjundas G, Dalal P, Damasceno A et al (2007) Standard method for developing stroke registers in low-income and middle-income countries: experiences from a feasibility study of a stepwise approach to stroke surveillance (STEPS Stroke). Lancet Neurol 6(2):134–139

    Article  CAS  PubMed  Google Scholar 

  2. Langhorne P, Coupar F, Pollock A (2009) Motor recovery after stroke: a systematic review. Lancet Neurol 8(8):741–754

    Article  PubMed  Google Scholar 

  3. Elkind MS, Sacco RL (1998) Stroke risk factors and stroke prevention. Semin Neurol 18(4):429–440

    Article  CAS  PubMed  Google Scholar 

  4. Sacco RL (2001) Newer risk factors for stroke. Neurology 57(5 Suppl 2):S31–S34

    Article  CAS  PubMed  Google Scholar 

  5. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG et al (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10(1):111–113

    Article  CAS  PubMed  Google Scholar 

  6. Djousse L, Himali JJ, Beiser A, Kelly-Hayes M, Wolf PA (2009) Apolipoprotein e, alcohol consumption, and risk of ischemic stroke: The Framingham Heart Study revisited. J Stroke Cerebrovasc Dis 18(5):384–388

    Article  PubMed Central  PubMed  Google Scholar 

  7. Zee RY, Cook NR, Cheng S, Reynolds R, Erlich HA, Lindpaintner K et al (2004) Polymorphism in the P-selectin and interleukin-4 genes as determinants of stroke: a population-based, prospective genetic analysis. Hum Mol Genet 13(4):389–396

    Article  CAS  PubMed  Google Scholar 

  8. Guo X (2014) Endothelial nitric oxide (eNOS) gene G894T and VNTR polymorphisms are closely associated with the risk of ischemic stroke development for Asians: meta-analysis of epidemiological studies. Mol Biol Rep 41(4):2571–2583

    Article  CAS  PubMed  Google Scholar 

  9. Szolnoki Z, Somogyvari F, Szabo M, Fodor L (2000) A clustering of unfavourable common genetic mutations in stroke cases. Acta Neurol Scand 102(2):124–128

    Article  CAS  PubMed  Google Scholar 

  10. 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(1):130–137

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Manso H, Krug T, Sobral J, Albergaria I, Gaspar G, Ferro JM et al (2010) Variants of the matrix metalloproteinase-2 but not the matrix metalloproteinase-9 genes significantly influence functional outcome after stroke. BMC Med Genet 11:40

    Article  PubMed Central  PubMed  Google Scholar 

  12. Park SY, Kim MH, Kang SY, Suh JT, Lee WI (2007) Inflammatory marker expression and its implication in Korean ischemic stroke patients. Korean J Lab Med 27(3):197–204

    Article  CAS  PubMed  Google Scholar 

  13. Fridman R, Toth M, Chvyrkova I, Meroueh SO, Mobashery S (2003) Cell surface association of matrix metalloproteinase-9 (gelatinase B). Cancer Metastasis Rev 22(2–3):153–166

    Article  CAS  PubMed  Google Scholar 

  14. Malemud CJ (2006) Matrix metalloproteinases (MMPs) in health and disease: an overview. Front Biosci 11:1696–1701

    Article  CAS  PubMed  Google Scholar 

  15. Maier CM, Hsieh L, Yu F, Bracci P, Chan PH (2004) Matrix metalloproteinase-9 and myeloperoxidase expression: quantitative analysis by antigen immunohistochemistry in a model of transient focal cerebral ischemia. Stroke 35(5):1169–1174

    Article  CAS  PubMed  Google Scholar 

  16. Rosell A, Ortega-Aznar A, Alvarez-Sabin J, Fernandez-Cadenas I, Ribo M, Molina CA et al (2006) Increased brain expression of matrix metalloproteinase-9 after ischemic and hemorrhagic human stroke. Stroke 37(6):1399–1406

    Article  CAS  PubMed  Google Scholar 

  17. Castellanos M, Leira R, Serena J, Pumar JM, Lizasoain I, Castillo J et al (2003) Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke. Stroke 34(1):40–46

    Article  CAS  PubMed  Google Scholar 

  18. Fornage M, Mosley TH, Jack CR, de Andrade M, Kardia SL, Boerwinkle E et al (2007) Family-based association study of matrix metalloproteinase-3 and -9 haplotypes with susceptibility to ischemic white matter injury. Hum Genet 120(5):671–680

    Article  CAS  PubMed  Google Scholar 

  19. Ye S (2000) Polymorphism in matrix metalloproteinase gene promoters: implication in regulation of gene expression and susceptibility of various diseases. Matrix Biol 19(7):623–629

    Article  CAS  PubMed  Google Scholar 

  20. Yasmin, McEniery CM, O’Shaughnessy KM, Harnett P, Arshad A, Wallace S et al. (2006) Variation in the human matrix metalloproteinase-9 gene is associated with arterial stiffness in healthy individuals. Arterioscler Thromb Vasc Biol 26(8):1799–1805.

  21. Hou L, Liu X, Li H, Kang J, LinHua Y (2009) Polymorphism of matrix metalloproteinase-9 related to cerebral infarction. Chin Rem Clin 9(7):575–577 (in Chinese).

  22. Montaner J, Fernandez-Cadenas I, Molina CA, Monasterio J, Arenillas JF, Ribo M et al (2003) Safety profile of tissue plasminogen activator treatment among stroke patients carrying a common polymorphism (C-1562T) in the promoter region of the matrix metalloproteinase-9 gene. Stroke 34(12):2851–2855

    Article  CAS  PubMed  Google Scholar 

  23. Szczudlik P, Borratynska A (2010) Association between the −1562 C/T MMP-9 polymorphism and cerebrovascular disease in a Polish population. Neurol Neurochir Pol 44(4):350–357

    CAS  PubMed  Google Scholar 

  24. Zhang B, Dhillon S, Geary I, Howell WM, Iannotti F, Day IN et al (2001) Polymorphisms in matrix metalloproteinase-1, -3, -9, and -12 genes in relation to subarachnoid hemorrhage. Stroke 32(9):2198–2202

    Article  CAS  PubMed  Google Scholar 

  25. Liu D, Yang J, Guang Z, Wu W, LiE P, Wang Y et al (2011) Study on polymorphisms of matrix metalioproteinase-2 and-9 genes of stroke patients. Chin J Geriatr Heart Brain Vessel Dis. 13(10):901–904

    CAS  Google Scholar 

  26. Zhou J, Liu J (2009) Matrix metalloproteinase-9 polymorphism(C1562T) in patients with cerebral infarction. China J Mod Med 19(12):1829–1831 (in Chinese)

    CAS  Google Scholar 

  27. Na S, Li W, LiYun S, YongAn Z, YuXin LI, GuangLai L (2011) A study of the association between polymorphism of MMP-9 gene and atherosclerosis and cerebral infarction. Chin J Clin Neurosci 19(5):476–480 (in Chinese)

    Google Scholar 

  28. Zhang L, Zhang Y, Li J, XiaoLei Z (2008) Relationship between the gene polymorphism of matrixmetalloproteinase-9/C1562T and ischemic stroke. J Clin Neurol 21(6):425–7 (in Chinese).

  29. Li J, Wu H, Li H, ShuGang H, Ying S, Chang Z et al (2013) Association between gene polymorphism of ALOX5AP, COX 2, MMP 9 and ischemic stroke. Med J Qilu 28(4):321–324 (in Chinese)

    Google Scholar 

  30. Jones CB, Sane DC, Herrington DM (2003) Matrix metalloproteinases: a review of their structure and role in acute coronary syndrome. Cardiovasc Res 59(4):812–823

    Article  CAS  PubMed  Google Scholar 

  31. Loftus IM, Naylor AR, Goodall S, Crowther M, Jones L, Bell PR et al (2000) Increased matrix metalloproteinase-9 activity in unstable carotid plaques. A potential role in acute plaque disruption. Stroke 31(1):40–47

    Article  CAS  PubMed  Google Scholar 

  32. 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(12):1579–1585

    Article  CAS  PubMed  Google Scholar 

  33. Gu Z, Cui J, Brown S, Fridman R, Mobashery S, Strongin AY et al (2005) A highly specific inhibitor of matrix metalloproteinase-9 rescues laminin from proteolysis and neurons from apoptosis in transient focal cerebral ischemia. J Neurosci 25(27):6401–6408

    Article  CAS  PubMed  Google Scholar 

  34. St-Pierre Y, Couillard J, Van Themsche C (2004) Regulation of MMP-9 gene expression for the development of novel molecular targets against cancer and inflammatory diseases. Expert Opin Ther Targets. 8(5):473–489

    Article  CAS  PubMed  Google Scholar 

  35. 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(14):1788–1794

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the Natural Science Foundation of Gansu Province (Grant No. 1107RJZA082).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Neurology, Second Hospital of Lanzhou University, No. 82 Cuiyingmen, Chengguan District, Lanzhou, 730030, Gansu, China

    Zhen-Zhen Fan, Zhao-Ming Ge, Hong-Bin Cai, Zhi-Yan Liu, Pei Liu & Hao-Yue Wang

Authors
  1. Zhen-Zhen Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhao-Ming Ge
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hong-Bin Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhi-Yan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hao-Yue Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhao-Ming Ge.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fan, ZZ., Ge, ZM., Cai, HB. et al. Association between the MMP-9−1562 C>T polymorphism and the risk of stroke: a meta-analysis. Mol Biol Rep 41, 6787–6794 (2014). https://doi.org/10.1007/s11033-014-3564-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-014-3564-0

Keywords

Search

Navigation