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

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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Correspondence to J E Tanus-Santos.

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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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