Department of Pharmacology, Faculty of Medicinal Sciences, State University of Campinas, Campinas, SP, Brazil.
Basic Clin Pharmacol Toxicol. 2012 Oct;111(4):262-7. doi: 10.1111/j.1742-7843.2012.00905.x. Epub 2012 Jun 27.
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.
基质金属蛋白酶(MMP)表达失衡,包括 MMP-2,已在子痫前期中得到证实。然而,关于 MMP-2 基因多态性对妊娠高血压疾病的影响知之甚少。我们研究了两种功能性 MMP-2 多态性(g.-1306C>T 和 g.-735C>T)是否与子痫前期和/或妊娠高血压有关,以及这些多态性是否影响这些疾病女性的治疗反应。我们研究了 216 名健康孕妇(HP)、185 名妊娠高血压(GH)患者和 216 名子痫前期(PE)患者。根据治疗反应的临床和实验室参数,将他们分为对降压治疗有反应和无反应的亚组。从全血中提取基因组 DNA,并使用 Taqman 等位基因区分检测法通过实时 PCR 确定 g-1306C>T 和 g.-735C>T 多态性的基因型。使用 PHASE 2.1 程序推断单倍型频率。在 HP、GH 和 PE 患者中,MMP-2 基因型和单倍型的分布相似(p > 0.05)。此外,当 GH 或 PE 患者被分类为对降压治疗有反应或无反应时,我们没有发现 MMP-2 基因型或单倍型频率的显著差异(p > 0.05)。我们的结果表明,MMP-2 多态性不影响妊娠高血压疾病的易感性。同时,MMP-2 多态性显然不影响这些妊娠高血压疾病女性对降压治疗的反应性。