title: Matrix metalloproteinase-9 polymorphisms affect plasma MMP-9 levels and antihypertensive therapy responsiveness in hypertensive disorders of pregnancy.
abstract: Abnormal matrix metalloproteinase (MMP)-9 levels may have a role in hypertensive disorders of pregnancy. We examined whether MMP-9 genetic polymorphisms (g.-1562C >T and g.-90(CA)13-25) modify plasma MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 levels and the responses to antihypertensive therapy in 214 patients with preeclampsia (PE), 185 patients with gestational hypertension (GH) and a control group of 214 healthy pregnant (HP). Alleles for the g.-90(CA)13-25 polymorphism were grouped L (low) (< 21 CA repeats) or H (high) (≥ 21 CA repeats). Plasma MMP-9 and TIMP-1 concentrations were measured by enzyme-linked immunosorbent assay. Plasma MMP-9 concentrations were not affected by genotypes or haplotypes in HP and PE groups, except for the g.-90(CA)13-25 polymorphism: GH patients with the LH genotype for this polymorphism have higher MMP-9 levels than those with other genotypes. The T allele for the g.-1562C > T polymorphism and the H4 haplotype (combining T and H alleles) are associated with GH and lack of responsiveness to antihypertensive therapy in GH. The H2 haplotype (combining C and H alleles) was associated with lack of responsiveness to antihypertensive therapy in PE, but not in GH. In conclusion, our results show that MMP-9 genetic variants are associated with GH and suggest that MMP-9 haplotypes affect the responsiveness to antihypertensive therapy in hypertensive disorders of pregnancy.
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, Sao Paulo, Brazil.
authors.forename: A C T
authors.initials: AC
authors.lastname: Palei
authors.forename: V C
authors.initials: VC
authors.lastname: Sandrim
authors.forename: L M
authors.initials: LM
authors.lastname: Amaral
authors.forename: J S R
authors.initials: JS
authors.lastname: Machado
authors.forename: R C
authors.initials: RC
authors.lastname: Cavalli
authors.forename: R
authors.initials: R
authors.lastname: Lacchini
authors.forename: G
authors.initials: G
authors.lastname: Duarte
authors.forename: J E
authors.initials: JE
authors.lastname: Tanus-Santos
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000235:genetics*; D011225:Pre-Eclampsia / Q000201:enzymology / Q000235:genetics; D011247:Pregnancy; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
chemical_list: D000959:Antihypertensive Agents; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9