title: Tissue inhibitor of matrix metalloproteinase-1 polymorphism, plasma TIMP-1 levels, and antihypertensive therapy responsiveness in hypertensive disorders of pregnancy.
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.
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: AC
authors.lastname: Palei
authors.affiliation: Department of Pharmacology, Institute of Biosciences, UniversidadeEstadual 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: L M
authors.initials: LM
authors.lastname: Amaral
authors.affiliation: Department of Gynecology and Obstetrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
authors.forename: J S R
authors.initials: JS
authors.lastname: Machado
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, 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: R C
authors.initials: RC
authors.lastname: Cavalli
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 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: D000328:Adult; D000483:Alleles; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics*; D011247:Pregnancy; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood* / Q000235:genetics* / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1