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Gene–gene interactions in the NAMPT pathway, plasma visfatin/NAMPT levels, and antihypertensive therapy responsiveness in hypertensive disorders of pregnancy

The Pharmacogenomics Journal volume 17, pages 427–434 (2017)Cite this article

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Abstract

Nicotinamide phosphorybosil transferase (NAMPT) polymorphisms affect visfatin/NAMPT levels and may affect the responsiveness to therapy in hypertensive disorders of pregnancy. We examined whether NAMPT polymorphisms (rs1319501 T>C and rs3801266 A>G), or haplotypes, and gene–gene interactions in the NAMPT pathway affect plasma visfatin/NAMPT levels and the response to antihypertensive therapy in 205 patients with preeclampsia (PE) and 174 patients with gestational hypertension. We also studied 207 healthy pregnant controls. Plasma visfatin/NAMPT levels were measured by ELISA. Non-responsive PE patients with the TC+CC genotypes for the rs1319501 T>C, and with the AG+GG genotypes for the rs3801266 A>G polymorphism had lower and higher visfatin/NAMPT levels, respectively. The ‘C, A’ haplotype was associated with response to antihypertensive therapy, and with lower visfatin/NAMPT levels in PE. Interactions among NAMPT, TIMP-1 and MMP-2 genotypes were associated with PE and with lack of response to antihypertensive therapy in PE. Our results suggest that NAMPT polymorphisms affect plasma visfatin/NAMPT levels in nonresponsive PE patients, and that gene–gene interactions in the NAMPT pathway not only promote PE but also decrease the response to antihypertensive therapy in PE.

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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). MRL is a Young Talent Attraction fellow from CNPq-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, V A Belo, L M Amaral & 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 Psychiatric Nursing and Human Sciences, Ribeirao Preto College of Nursing, University of São Paulo, Sao Paulo, Brazil

    R Lacchini

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

    G Duarte & R C Cavalli

  5. Department of Pharmacology, Institute of Biosciences, Universidade Estadual Paulista (UNESP), Botucatu, Sao Paulo, Brazil

    V C Sandrim

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  1. M R Luizon
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Luizon, M., Palei, A., Belo, V. et al. Gene–gene interactions in the NAMPT pathway, plasma visfatin/NAMPT levels, and antihypertensive therapy responsiveness in hypertensive disorders of pregnancy. Pharmacogenomics J 17, 427–434 (2017). https://doi.org/10.1038/tpj.2016.35

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