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Tissue inhibitor of matrix metalloproteinase-1 polymorphism, plasma TIMP-1 levels, and antihypertensive therapy responsiveness in hypertensive disorders of pregnancy

The Pharmacogenomics Journal volume 14, pages 535–541 (2014)Cite this article

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Abstract

Tissue inhibitor of metalloproteinase (TIMP)-1 is a major endogenous inhibitor of matrix metalloproteinase (MMP)-9, which may affect the responsiveness to therapy in hypertensive disorders of pregnancy. We examined whether TIMP-1 polymorphism (g.–9830T>G, rs2070584) modifies plasma MMP-9 and TIMP-1 levels and the response to antihypertensive therapy in 596 pregnant: 206 patients with preeclampsia (PE), 183 patients with gestational hypertension (GH) and 207 healthy pregnant controls. We also studied the TIMP-3 polymorphism (g.–1296T>C, rs9619311). Plasma MMP-9 and TIMP-1 levels were measured by ELISA. GH patients with the GG genotype for the TIMP-1 polymorphism had lower MMP-9 levels and MMP-9/TIMP-1 ratios than those with the TT genotype. PE patients with the TG genotype had higher TIMP-1 levels. The G allele and the GG genotype were associated with PE and responsiveness to antihypertensive therapy in PE, but not in GH. Our results suggest that the TIMP-1 g.–9830T>G polymorphism not only promotes PE but also decreases the responses to antihypertensive therapy.

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Acknowledgements

This study was funded by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-Brazil), the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-Brazil) and the Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP-Brazil).

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Authors and Affiliations

  1. Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

    M R Luizon, L M Amaral, R Lacchini & J E Tanus-Santos

  2. Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA

    A C T Palei

  3. Department of Pharmacology, Institute of Biosciences, UniversidadeEstadual Paulista (UNESP), Botucatu, Sao Paulo, Brazil

    V C Sandrim

  4. Department of Gynecology and Obstetrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

    J S R Machado, R C Cavalli & G Duarte

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  1. M R Luizon
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Correspondence to J E Tanus-Santos.

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Luizon, M., Palei, A., Sandrim, V. et al. Tissue inhibitor of matrix metalloproteinase-1 polymorphism, plasma TIMP-1 levels, and antihypertensive therapy responsiveness in hypertensive disorders of pregnancy. Pharmacogenomics J 14, 535–541 (2014). https://doi.org/10.1038/tpj.2014.26

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