Rahimi Ziba, Lotfi Sarah, Ahmadi Abbas, Jalilian Nasrin, Shakiba Ebrahim, Vaisi-Raygani Asad, Rahimi Zohreh
a Medical Biology Research Center , Kermanshah University of Medical Sciences , Kermanshah , Iran.
b Department of Obstetrics and Gynaecology , Kermanshah University of Medical Sciences , Kermanshah , Iran.
J Obstet Gynaecol. 2018 Apr;38(3):327-332. doi: 10.1080/01443615.2017.1354178. Epub 2017 Oct 10.
Matrix metalloproteinase (MMP) -2 C-735 T and MMP-7 A-181 G genotypes were studied in 144 pregnant patients with mild and severe preeclampsia and 103 healthy pregnant women. Significantly higher frequencies of CT and TT genotypes in patients compared to controls increased the risk of preeclampsia by 2.42 and 3.13 times, respectively. In severe preeclamptic women in the presence of MMP-2 CT the level of total antioxidant capacity was significantly lower than MMP-2 CC genotype. Also, in the presence of MMP-2 CT + TT blood pressure was significantly increased compared to CC genotype in all the patients. The combined presence of MMP-2 T and the MMP-7 A alleles compared to MMP-2 C and MMP-7 A alleles significantly increased the risk of preeclampsia by 3.08-fold. Our findings demonstrate an association between the MMP-2 C-735 T polymorphism with blood pressure and the risk of preeclampsia. Also, in the presence of polymorphism total antioxidant capacity level decreased in severe preeclampsia. Impact statement What is already known on this subject: Matrix metalloproteinases (MMPs) including MMP-2 might be involved in the pathogenesis of preeclampsia through alteration of invasive ability of trophoblastic cells and abnormal placentation. In one available study the absence of association between MMP-2 C-735T polymorphism with gestational hypertension or preeclampsia has been reported. What the results of this study add: We found that the presence of MMP-2 C-735T polymorphism increased the risk of preeclampsia and there was a significantly lower level of total antioxidant capacity in the presence of the polymorphism in severe preeclampsia. Also, we found significantly higher systolic and diastolic blood pressures in the presence of MMP-2 C-735T polymorphism. We detected a synergism between the MMP-2 T and the MMP-7 A alleles that increased the risk of preeclampsia. What the implications are of these findings for clinical practice and/or further research: New findings of our study are involvement of lower activity MMP-2 -735 T allele and its synergism with MMP-7 A allele, low promoter activity allele, in the pathogenesis of preeclampsia through possible impairment of placentation and also by decreased total antioxidant capacity and increased blood pressure. Further association studies of the role of MMP-2 polymorphism and MMP-2 activity in relation to oxidative stress parameters and blood pressure could elucidate the role of MMP-2 and MMP-7 in the pathogenesis of preeclampsia.
对144例轻度和重度子痫前期孕妇及103例健康孕妇进行了基质金属蛋白酶（MMP）-2 C-735T和MMP-7 A-181G基因型研究。与对照组相比，患者中CT和TT基因型的频率显著更高，子痫前期风险分别增加2.42倍和3.13倍。在重度子痫前期女性中，存在MMP-2 CT时，总抗氧化能力水平显著低于MMP-2 CC基因型。此外，在所有患者中，存在MMP-2 CT+TT时，血压相较于CC基因型显著升高。与MMP-2 C和MMP-7 A等位基因相比，MMP-2 T和MMP-7 A等位基因共同存在时，子痫前期风险显著增加3.08倍。我们的研究结果表明MMP-2 C-735T多态性与血压及子痫前期风险之间存在关联。此外，在存在多态性时，重度子痫前期患者的总抗氧化能力水平降低。影响声明：关于该主题已有的了解：包括MMP-2在内的基质金属蛋白酶可能通过改变滋养层细胞的侵袭能力和异常胎盘形成参与子痫前期的发病机制。在一项现有研究中，已报道MMP-2 C-735T多态性与妊娠期高血压或子痫前期之间无关联。本研究结果补充了什么：我们发现存在MMP-2 C-735T多态性会增加子痫前期风险，且在重度子痫前期存在该多态性时总抗氧化能力水平显著降低。此外，我们发现存在MMP-2 C-735T多态性时收缩压和舒张压显著更高。我们检测到MMP-2 T和MMP-7 A等位基因之间存在协同作用，增加了子痫前期风险。这些发现对临床实践和/或进一步研究有何意义：我们研究的新发现是低活性的MMP-2 -735 T等位基因及其与MMP-7 A等位基因（低启动子活性等位基因）的协同作用，可能通过胎盘形成受损、总抗氧化能力降低和血压升高参与子痫前期的发病机制。关于MMP-2多态性和MMP-2活性与氧化应激参数及血压关系的进一步关联研究，可能会阐明MMP-2和MMP-7在子痫前期发病机制中的作用。
