Volume 93, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Phagocytosis of malaria pigment (hemozoin) induces increased activity of matrix metalloproteinase (MMP)-9, an endopeptidase involved in cytokine regulation. In this study, we examined whether a common functional promoter polymorphism (rs3918242) affects infection in pregnancy. Eighteen percent of Ghanaian primiparae carried the minor allele. It was associated with reduced odds of placental hemozoin and of placental as well as peripheral blood parasitemia. The results indicate that a common polymorphism protects against placental malaria indicating that this endopeptidase is involved in susceptibility to .


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  1. Desai M, ter Kuile FO, Nosten F, McGready R, Asamoa K, Brabin B, Newman RD, , 2007. Epidemiology and burden of malaria in pregnancy. Lancet Infect Dis 7: 93104.[Crossref] [Google Scholar]
  2. Mockenhaupt FP, Bedu-Addo G, von Gaertner C, Boye R, Fricke K, Hannibal I, Karakaya F, Schaller M, Ulmen U, Acquah PA, Dietz E, Eggelte TA, Bienzle U, , 2006. Detection and clinical manifestation of placental malaria in southern Ghana. Malar J 5: 119.[Crossref] [Google Scholar]
  3. Rogerson SJ, Hviid L, Duffy PE, Leke RF, Taylor DW, , 2007. Malaria in pregnancy: pathogenesis and immunity. Lancet Infect Dis 7: 105117.[Crossref] [Google Scholar]
  4. Bedu-Addo G, Meese S, Mockenhaupt FP, , 2013. An ATP2B4 polymorphism protects against malaria in pregnancy. J Infect Dis 207: 16001603.[Crossref] [Google Scholar]
  5. Lopez C, Saravia C, Gomez A, Hoebeke J, Patarroyo MA, , 2010. Mechanisms of genetically-based resistance to malaria. Gene 467: 112.[Crossref] [Google Scholar]
  6. Page-McCaw A, Ewald AJ, Werb Z, , 2007. Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol 8: 221233.[Crossref] [Google Scholar]
  7. Van Lint P, Libert C, , 2007. Chemokine and cytokine processing by matrix metalloproteinases and its effect on leukocyte migration and inflammation. J Leukoc Biol 82: 13751381.[Crossref] [Google Scholar]
  8. Griffiths MJ, Shafi MJ, Popper SJ, Hemingway CA, Kortok MM, Wathen A, Rockett KA, Mott R, Levin M, Newton CR, Marsh K, Relman DA, Kwiatkowski DP, , 2005. Genomewide analysis of the host response to malaria in Kenyan children. J Infect Dis 191: 15991611.[Crossref] [Google Scholar]
  9. Prato M, Giribaldi G, Polimeni M, Gallo V, Arese P, , 2005. Phagocytosis of hemozoin enhances matrix metalloproteinase-9 activity and TNF-alpha production in human monocytes: role of matrix metalloproteinases in the pathogenesis of falciparum malaria. J Immunol 175: 64366442.[Crossref] [Google Scholar]
  10. D'Alessandro S, Basilico N, Prato M, , 2013. Effects of Plasmodium falciparum-infected erythrocytes on matrix metalloproteinase-9 regulation in human microvascular endothelial cells. Asian Pac J Trop Med 6: 195199.[Crossref] [Google Scholar]
  11. Zhang B, Ye S, Herrmann SM, Eriksson P, de Maat M, Evans A, Arveiler D, Luc G, Cambien F, Hamsten A, Watkins H, Henney AM, , 1999. Functional polymorphism in the regulatory region of gelatinase B gene in relation to severity of coronary atherosclerosis. Circulation 99: 17881794.[Crossref] [Google Scholar]
  12. Ye S, , 2000. Polymorphism in matrix metalloproteinase gene promoters: implication in regulation of gene expression and susceptibility of various diseases. Matrix Biol 19: 623629.[Crossref] [Google Scholar]
  13. El Samanoudy A, Monir R, Badawy A, Ibrahim L, Farag K, El Baz S, Alenizi D, Alenezy A, , 2014. Matrix metalloproteinase-9 gene polymorphism in hepatocellular carcinoma patients with hepatitis B and C viruses. Genet Mol Res 13: 80258034.[Crossref] [Google Scholar]
  14. Snounou G, Viriyakosol S, Zhu XP, Jarra W, Pinheiro L, do Rosario VE, Thaithong S, Brown KN, , 1993. High sensitivity of detection of human malaria parasites by the use of nested polymerase chain reaction. Mol Biochem Parasitol 61: 315320.[Crossref] [Google Scholar]
  15. Eggelte TA, Navaratnam V, Payne D, , 1990. Production of monoclonal antibodies against antimalarial drugs for use in immunoassays. , eds. The Validation of Chemial and Immunochemical Tests for Antimalarials in Body Fluids, International Monograph Series 3. Penang, Malaysia: Universiti Sains Malaysia, 3563. [Google Scholar]
  16. Finnstrom O, , 1977. Studies on maturity in newborn infants. IX. Further observations on the use of external characteristics in estimating gestational age. Acta Paediatr Scand 66: 601604.[Crossref] [Google Scholar]
  17. Coolman M, de Maat M, Van Heerde WL, Felida L, Schoormans S, Steegers EA, Bertina RM, de Groot CJ, , 2007. Matrix metalloproteinase-9 gene-1562C/T polymorphism mitigates preeclampsia. Placenta 28: 709713.[Crossref] [Google Scholar]
  18. Geurts N, Opdenakker G, Van den Steen PE, , 2012. Matrix metalloproteinases as therapeutic targets in protozoan parasitic infections. Pharmacol Ther 133: 257279.[Crossref] [Google Scholar]
  19. Lucchi NW, Peterson DS, Moore JM, , 2008. Immunologic activation of human syncytiotrophoblast by Plasmodium falciparum . Malar J 7: 42.[Crossref] [Google Scholar]
  20. Xu P, Alfaidy N, Challis JR, , 2002. Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in human placenta and fetal membranes in relation to preterm and term labor. J Clin Endocrinol Metab 87: 13531361.[Crossref] [Google Scholar]
  21. Winberg JO, Kolset SO, Berg E, Uhlin-Hansen L, , 2000. Macrophages secrete matrix metalloproteinase 9 covalently linked to the core protein of chondroitin sulphate proteoglycans. J Mol Biol 304: 669680.[Crossref] [Google Scholar]
  22. Muehlenbachs A, Fried M, McGready R, Harrington WE, Mutabingwa TK, Nosten F, Duffy PE, , 2010. A novel histological grading scheme for placental malaria applied in areas of high and low malaria transmission. J Infect Dis 202: 16081616.[Crossref] [Google Scholar]

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  • Received : 18 Dec 2014
  • Accepted : 25 Mar 2015
  • Published online : 08 Jul 2015

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