Matrix metalloproteinase-7 A-181G and its interaction with matrix metalloproteinase-9 C-1562T polymorphism in preeclamptic patients: association with malondialdehyde level and severe preeclampsia.
Objective: The abnormal activation of matrix metalloproteinases (MMPs) during pregnancy might be involved in the pathogenesis of preeclampsia. The aim of present study was to investigate the possible influence of MMP-7 A-181G and its interaction with MMP-9 C- 1562T polymorphism on the risk of preeclampsia and lipid peroxidation level.
Methods: In a case-control study the MMP-7 A-181G and MMP-9 C-1562T polymorphisms were studied in 168 preeclamptic and 154 healthy pregnant women from Western Iran. The MMP-7 and-9 genotypes were detected using polymerase chain reaction-restriction fragment length polymorphism method.
Results: The frequency of MMP-7 G allele in mild- (37.4 %) and severe-preeclampsia (45.6 %) and controls (40.3 %) were not significantly different. In preeclamptic patients in the presence of MMP-7 AG + GG genotype there was a significantly higher concentration of malondialdehyde (MDA) (10.52 ± 4.18 μM, p = 0.017) compared to that in AA genotype carriers (9 ± 2.89 μM). Also, in the presence of both MMP-7 G and MMP-9 T alleles the MDA concentration (11.6 ± 4.9 μM) was significantly higher compared to the concomitant presence of MMP-7 A and MMP-9 C wild alleles (9.2 ± 3.1 μM, p = 0.02). There was an interaction between two alleles of MMP-7 G and MMP-9 T that significantly increased the risk of severe preeclampsia by 1.4-fold (OR = 1.4, 95 % CI = 1.06-1.85, p = 0.016).
Conclusions: The present study indicates lack of a direct influence of MMP-7 A-181G polymorphism on the risk of preeclampsia. However, this polymorphism through elevation of MDA level as a marker of lipid peroxidation and interaction with MMP-9 C-1562T polymorphism might be associated with the risk of severe preeclampsia.