Luizon M R, Palei A C T, Sandrim V C, Amaral L M, Machado J S R, Lacchini R, Cavalli R C, Duarte G, Tanus-Santos J E
Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.
Pharmacogenomics J. 2014 Dec;14(6):535-41. doi: 10.1038/tpj.2014.26. Epub 2014 Jun 24.
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.
金属蛋白酶组织抑制剂（TIMP）-1是基质金属蛋白酶（MMP）-9的主要内源性抑制剂，其可能影响妊娠期高血压疾病的治疗反应性。我们检测了596名孕妇中TIMP-1基因多态性（g.-9830T>G，rs2070584）是否会改变血浆MMP-9和TIMP-1水平以及对抗高血压治疗的反应：206例先兆子痫（PE）患者、183例妊娠期高血压（GH）患者和207名健康孕妇对照。我们还研究了TIMP-3基因多态性（g.-1296T>C，rs9619311）。采用酶联免疫吸附测定法检测血浆MMP-9和TIMP-1水平。TIMP-1基因多态性为GG基因型的GH患者，其MMP-9水平和MMP-9/TIMP-1比值低于TT基因型患者。TG基因型的PE患者TIMP-1水平较高。G等位基因和GG基因型与PE以及PE患者对抗高血压治疗的反应性相关，但与GH无关。我们的结果表明，TIMP-1 g.-9830T>G基因多态性不仅会促进PE的发生，还会降低对抗高血压治疗的反应。
