title: 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.
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
authors.forename: M R
authors.initials: MR
authors.lastname: Luizon
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: A C T
authors.initials: ACT
authors.lastname: Palei
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
authors.forename: V A
authors.initials: VA
authors.lastname: Belo
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
authors.forename: L M
authors.initials: LM
authors.lastname: Amaral
authors.affiliation: Department of Psychiatric Nursing and Human Sciences, Ribeirao Preto College of Nursing, University of São Paulo, Sao Paulo, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Lacchini
authors.affiliation: Department of Gynecology and Obstetrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
authors.forename: G
authors.initials: G
authors.lastname: Duarte
authors.affiliation: Department of Gynecology and Obstetrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
authors.forename: R C
authors.initials: RC
authors.lastname: Cavalli
authors.affiliation: Department of Pharmacology, Institute of Biosciences, Universidade Estadual Paulista (UNESP), Botucatu, Sao Paulo, Brazil.
authors.forename: V C
authors.initials: VC
authors.lastname: Sandrim
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
authors.forename: J E
authors.initials: JE
authors.lastname: Tanus-Santos
mesh_terms: D000959:Antihypertensive Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood* / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D054409:Nicotinamide Phosphoribosyltransferase / Q000097:blood* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D011247:Pregnancy; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D016207:Cytokines; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2