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A genetic polymorphism of matrix metalloproteinase 9 (MMP-9) affects the changes in circulating MMP-9 levels induced by highly active antiretroviral therapy in HIV patients

The Pharmacogenomics Journal volume 9, pages 265–273 (2009)Cite this article

Abstract

We examined whether two functional polymorphisms (g.−1562C>T and g.−90(CA)14–24) in the matrix metalloproteinase (MMP)-9 gene or MMP-9 haplotypes affect the circulating levels of pro-MMP-9 and pro-MMP-9/TIMP-1 (tissue inhibitor of metalloproteinase-1) ratios in AIDS patients, and modulate alterations in these biomarkers after highly active antiretroviral therapy (HAART). We studied 82 patients commencing HAART. Higher pro-MMP-9 concentrations and pro-MMP-9/TIMP-1 ratios were found in CT/TT patients compared with CC patients. HAART decreased pro-MMP-9 levels and pro-MMP-9/TIMP-1 ratios in CT/TT patients, it did not modify pro-MMP-9 levels and it increased pro-MMP-9/TIMP-1 ratios in CC patients. The g.−90(CA)14–24 polymorphism, however, produced no significant effects. Moreover, we found no significant differences in HAART-induced changes in plasma pro-MMP-9, TIMP-1 and pro-MMP-9/TIMP-1 ratios when different MMP-9 haplotypes were compared. These findings suggest that the g.−1562C>T polymorphism affects pro-MMP-9 levels in patients with AIDS and modulates the alterations in pro-MMP-9 levels caused by HAART, thus possibly affecting the risk of cardiovascular complications.

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Acknowledgements

This study was supported by Fundação de Amparo à Pesquisa do Estado de Sao Paulo (FAPESP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, Ribeirao Preto, SP, Brazil

    C Demacq, V B Vasconcellos & J E Tanus-Santos

  2. Department of Morphology, Estomatology and Physiology, Dental School of Ribeirao Preto, University of Sao Paulo, Av. do Cafe, Ribeirao Preto, SP, Brazil

    A M Marcaccini & R F Gerlach

  3. Department of Medicine, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, Ribeirao Preto, SP, Brazil

    A A Machado

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Correspondence to J E Tanus-Santos.

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Demacq, C., Vasconcellos, V., Marcaccini, A. et al. A genetic polymorphism of matrix metalloproteinase 9 (MMP-9) affects the changes in circulating MMP-9 levels induced by highly active antiretroviral therapy in HIV patients. Pharmacogenomics J 9, 265–273 (2009). https://doi.org/10.1038/tpj.2009.13

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