Effects of matrix metalloproteinase (MMP)-2 polymorphisms on responsiveness to antihypertensive therapy of women with hypertensive disorders of pregnancy.

Abstract

Imbalanced matrix metalloproteinase (MMP) expression, including MMP-2, has been demonstrated in pre-eclampsia. However, little is known about the effect of polymorphisms in MMP-2 gene on hypertensive disorders of pregnancy. We examined whether two functional MMP-2 polymorphisms (g.-1306C>T and g.-735C>T) are associated with pre-eclampsia and/or gestational hypertension and whether these polymorphisms affect therapeutic responses in women with these conditions. We studied 216 healthy pregnant women (HP), 185 patients with gestational hypertension (GH) and 216 patients with pre-eclampsia (PE). They were stratified as responsive or non-responsive to antihypertensive therapy according to clinical and laboratorial parameters of therapeutic responsiveness. Genomic DNA was extracted from whole blood and genotypes for g-1306C>T and g.-735C>T polymorphisms were determined by real-time PCR using Taqman allele discrimination assays. Haplotype frequencies were inferred using the PHASE 2.1 program. The distributions of MMP-2 genotypes and haplotypes were similar in HP, GH and PE patients (p > 0.05). In addition, we found no significant differences in MMP-2 genotype or haplotype frequencies when GH or PE patients were classified as responsive or non-responsive to antihypertensive therapy (p > 0.05). Our results suggest that MMP-2 polymorphisms do not affect the susceptibility to hypertensive disorders of pregnancy. In parallel, MMP-2 polymorphisms apparently do not affect the responsiveness to antihypertensive therapy of women with these hypertensive disorders of pregnancy.

• Authors: Ana C T Palei, Valeria C Sandrim, Lorena M Amaral, Jackeline S R Machado, Ricardo C Cavalli, Riccardo Lacchini, Geraldo Duarte, Jose E Tanus-Santos
• Journal: Basic & clinical pharmacology & toxicology (Basic Clin Pharmacol Toxicol) Vol. 111 Issue 4 Pg. 262-7 (Oct 2012) ISSN: 1742-7843 [Electronic] England
• PMID: 22672240 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 The Authors Basic & Clinical Pharmacology & Toxicology © 2012 Nordic Pharmacological Society.

Chemical References

• Antihypertensive Agents
• Genetic Markers
• MMP2 protein, human
• Matrix Metalloproteinase 2

Topics

• Adolescent
• Adult
• Antihypertensive Agents (pharmacology)
• Female
• Gene Frequency
• Genetic Markers
• Genetic Predisposition to Disease
• Haplotypes
• Humans
• Hypertension, Pregnancy-Induced (drug therapy, genetics)
• Logistic Models
• Matrix Metalloproteinase 2 (genetics)
• Polymorphism, Genetic
• Pre-Eclampsia (drug therapy, genetics)
• Pregnancy
• Real-Time Polymerase Chain Reaction
• Young Adult