الفهرس 
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Abstract
The pursuit for a predictive biomarker for pre-eclampsia (PET) continues. Familial predispo-sition to pre-eclampsia, confirmed by epidemiological studies suggests an inherited genetic factor. Different candidate genes have been investigated in relation to association to pre-eclampsia. A novel potential candidate is angiopoietin-2 (ANGPT2) which is a vascular growth factor that binds to the endothelial cell-specific receptor. Human ANGPT2 has been found to be highly polymorphic. The most common polymorphism of ANGPT2 is a G/A pol-ymorphism which is detectable by Eco57l restriction enzyme cleavage. This polymorphism is thought to alter protein expression and might subsequently inhibit angiogenesis, and has al-ready been linked with recurrent miscarriages and unexplained intrauterine fetal death. Based on these findings and given the assumed anti-angiogenic biological role of ANGPT2, we hy-pothesized that a common polymorphism of ANGPT2 is associated with an increased inci-dence of pre-eclampsia in Egyptian women.
We conducted a case control study. We compared 60 Egyptian women with pre-eclampsia further subcategorized according to severity into mild PET (n=20), severe PET (n=20), ec-lampsia (n=10) and HELLP syndrome (n=10) with 30 women from the same ethnic group who had normal pregnancies, for the presence of the ANGPT2 polymorphism. Gene poly-morphism was evaluated using PCR restriction fragment length polymorphism (PCR-RFLP). Serum levels of Angiopoitien-2 was also plotted from cases and controls as well as markers for oxidative stress.
Results showed that there was no statistically significant difference in the distribution of the polymorphic ANGPT2 gene between preeclamptic patients and normal pregnant controls. Further subgroup analysis within patients group according to severity of pre-eclampsia as well as the occurrence of HELLP syndrome or eclamptic fits showed a trend towards the pol-ymorphic gene in the sever group yet this did not reach statistical significance.
Serum levels of angiopoietin-2 were significantly higher in cases than in controls. This was further intensified in the subjects with the polymorphic gene variant. Showing even higher correlation curves in the severe subgroups.
Similar association was identified with the markers of oxidative stress, where levels were sta-tistically significantly higher in the cases than the controls. The presence of the polymorphic ANGPT2 gene was again a factor towards a steeper association curves.
Angiopoitin-2 gene polymorphism is not directly associated with increased incidence of pre-eclampsia, it cannot be used as a tool for early prediction of pre-eclampsia. However, serum levels of angiopoietin-2 are significantly higher in pre-eclampsia patients than normal controls. The presence of the polymorphic gene intensifies the responsive release of angiopoietin-2 and seems to play a crucial role in the disease severity and increased oxidative stress response. This has the potential of targeting angiopoietin-2 pharmacologically as a potential disease modifying approach in pre-eclampsia. Yet this is a complex issue and needs further studies to assess its feasibility and safety.