Matrix metalloproteinase-2 C-735T and its interaction with matrix metalloproteinase-7 A-181G polymorphism are associated with the risk of preeclampsia: influence on total antioxidant capacity and blood pressure

Abstract

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.

Keyword:

• MMP-2 C-735T
• MMP-7 A-181G
• preeclampsia
• total antioxidant capacity
• blood pressure
• polymorphism

Acknowledgments

This work was performed in partial fulfilment of the requirements for MD degree of Dr. Sarah Lotfi and was financially supported by a grant from Vice Chancellor for Research of Kermanshah University of Medical Sciences, Kermanshah, Iran.

Disclosure statement

The authors report no declarations of interest.