Preeclampsia is a disease of pregnancy, thought to be unique to humans, that manifests itself as a clinical syndrome of hypertension, proteinuria, and edema after 20 weeks of gestation in a previously normotensive individual. The syndrome resolves after delivery, a fact that points to a prime role of the placenta in the etiology of the disease. Indeed, the presence of a fetus is not necessary for preeclampsia to develop; it occurs in molar pregnancy and removal of trophoblast resolves the disease.
Preeclampsia is the leading cause of maternal morbidity and mortality in underdeveloped countries. Although preeclampsia is a transient condition, woman who had preeclampsia or gestational hypertension are at increased risk of stroke and coronary artery disease. It is characterized by abnormal trophoblast invasion of the spiral arteries of the decidua and myometrium leading to a failure to establish an adequate uteroplacental blood flow and, therefore, is thought to give rise to relatively hypoxic trophoblast tissue. This, in turn, may promote an exaggerated state of oxidative stress in the placenta. This hypoxia/oxidative stress may then further attenuate trophoblast invasion but also alters placental villous angiogenesis leading to a poorly developed fetoplacental vasculature with abnormal reactivity.
Matrix metalloproteinases (MMPs) are a family of structurally related, zinc-dependent enzymes that break down several extracellular matrix components. Altered MMP activity has been reported in different clinical conditions that contributed to vascular system such as hypertensive disorders of pregnancy. Abnormal regulation of MMPs that is observed in hypertensive disorders of pregnancy may reflect abnormal invasive ability of trophoblastic cells, and upregulated MMPs with increased oxidative stress and inflammatory mediators may interact to produce endothelial cell dysfunction seen in preeclampsia and gestational hypertension.
Abnormal production of matrix metalloproteinases (MMPs), especially MMP-9, may play a role in hypertensive disorders of pregnancy. These alterations may result from functional genetic polymorphisms in the promoter region of MMP-9 gene, which are known to change MMP-9 expression. Genetic polymorphisms in the MMP-9 gene affect MMP-9 transcription, and two of them are functional: the g.−1562C>T substitution (rs3918242) and the microsatellite g.−90(CA)13–25 (rs3222264). These functional MMP-9 polymorphisms have been associated with different disease conditions, including cardiovascular diseases and severity of coronary atherosclerosis.
The purpose of the present study was to investigate whether the two functional polymorphisms (g.−1562C>T and g.−90(CA)13–25) in the MMP-9 gene, either alone or combined, are associated with gestational hypertension or preeclampsia.
In this work we studied 75 pregnant women: 25 healthy pregnant, 25 pregnant with gestational hypertension (GH), and 25 pregnant with preeclampsia (PE). Full clinical history (especially family and past history for miscarriage and preeclampsia) was taken from all subjects, if the patient was primigravida or multigravida, complete clinical examination (mainly blood pressure), U/S to determine the gestational age in weeks and laboratory investigations including estimation of HB level, detection of proteinuria and molecular studying for g.−1562C>T and g.−90(CA)13–25 polymorphisms in MMP-9 gene by PCR-RFLP and end point conventional PCR respectively.
For both g.−1562C>T and g.−90(CA)13–25 polymorphism, this study showed that, no significant differences were found in genotypes and alleles distributions when PE or GH groups were compared with healthy pregnant group. Also there is no significant differences were found in overall distributions of the four possible haplotype frequencies when the GH or the PE group was compared with the healthy pregnant group.
In conclusion, our limited study on a small group of Egyptian population demonstrated that MMP-9 -1562C/T and -90(CA)13-25 polymorphisms in addition to their haplotypes did not show significant deviation in GH or PE patients compared with normotensive pregnant women controls. Despite our findings, this cannot rule out the important role of MMP-9 in the development of hypertensive disorders of pregnancy.
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