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Τίτλος – Title
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Γονιδιακά Αίτια της Προεκλαμψίας |
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Συγγραφέας – Author(s)
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Αρτεμισία Κοκκινάρη1, Αικατερίνη Λυκερίδου2, Κλεάνθη Γουρουντή3, Γεώργιος Ιατράκης4 |
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Παραπομπή – Citation
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Κοκκινάρη Α., Λυκερίδου Α., Γουρουντή Κ., Ιατράκης Γ.: Γονιδιακά Αίτια της Προεκλαμψίας, Επιθεώρηση Κλιν. Φαρμακολ. Φαρμακοκινητ. 32(3): 173-178 (2014) |
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Ημερομηνία Δημοσιευσης – Publication Date
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1 Νοεμβρίου 2014 – 2014-11-01
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Γλώσσα Πλήρους Κειμένου –
Full Text Language |
Ελληνικά – Greek |
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Λέξεις κλειδιά – Keywords
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Προεκλαμψία, μη φυσιολογική πλακουντοποίηση, παθογενετικός μηχανισμός, γονίδια μητρικής και πατρικής ευαισθησίας, αντι-αγγειογόνες πρωτεΐνες, θεραπευτικές παρεμβάσεις
Preeclampsia, insufficient placentation, multifactorial pathogenesis, anti-vascular proteins, phenotypes, clinical management |
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Λοιποί Όροι – Other Terms
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άρθρο επισκόπησης |
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Περίληψη – Summary
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Η προεκλαμψία είναι ένα κλινικό σύνδρομο, που παρατηρείται στο 5% των κυήσεων και σχετίζεται με αυξημένα ποσοστά εμβρυϊκής και μητρικής νοσηρότητας και θνησιμότητας. Αυτή χαρακτηρίζεται από αρτηριακή υπέρταση, πρωτεϊνουρία και κάποιες φορές από διαταραχή της λειτουργίας διαφόρων οργάνων ποικίλης κλινικής βαρύτητας. Η μη φυσιολογική πλακουντοποίηση, η οποία συνοδεύεται από αυξημένη αντίσταση του αγγειακού δικτύου, ενεργοποίηση του μηχανισμού πήξης και δυσλειτουργία των ενδοθηλιακών κυττάρων, αποτελεί το βασικό παθογενετικό μηχανισμό της προεκλαμψίας. Μία σειρά γονιδίων μητρικής και πατρικής ευαισθησίας, καθώς και πολυμορφισμοί, έχουν ενοχοποιηθεί. Τέτοια γονίδια είναι τα FAS 670G, ACE, CTLA4, F2, F5, LPL, SERPINE1, NOS3, ACVR2A, STOX1, αλλά χρειάζεται περισσότερη έρευνα προκειμένου να διευκρινιστεί ο ακριβής ρόλος τους. Επίσης, το οξειδωτικό stress, με την απελευθέρωση ελευθέρων ριζών Ο2 και ONOO- και ο μεταβολισμός των λιπιδίων, κατέχουν εξέχοντα ρόλο στο εναρκτήριο λάκτισμα της προεκλαμψίας. Από τον πλακούντα, παράγονται επίσης δύο αντι-αγγειογόνες πρωτεΐνες, η sFlt1 και Seng. Η sFlt1 δεσμεύει τον VEGF παράγοντα, υπεύθυνο για την αγγειογένεση. Αυτοί οι παράγοντες μπορούν να χρησιμοποιηθούν στο μέλλον ως προγνωστικοί δείκτες σε συνδυασμό με Doppler των μητριαίων αγγείων. Το γεγονός ότι η προεκλαμψία είναι μία πολυπαραγοντική νόσος με ποικίλες φαινοτυπικές εκφάνσεις, καθιστά την πρώιμη διάγνωση, αλλά και την πρόληψη της νόσου, εξαιρετικά δύσκολη. Όσον αφορά, τέλος, στις θεραπευτικές παρεμβάσεις, αυτές παραμένουν ουσιαστικά συμπτωματικές και στοχεύουν στον περιορισμό της εμβρυϊκής και μητρικής νοσηρότητας και θνησιμότητας. Preeclampsia is a clinical syndrome which occurs in 5% of pregnancies and is associated with increased maternal and fetal mortality and morbidity. It is characterized by hypertension, proteinuria and sometimes by liver disorders and coagulation abnormalities. The pathogenesis of preeclampsia is still not fully elucidated. According to the current hypothesis the primary event is insufficient placentation causing endothelial dysfunction, vasospasm and activation of the coagulation cascade. A lot of genes have been criminated, such as FAS 670G, ACE, CTLA4, F2, F5, LPL, SERPINE1, NOS3, ACVR2A, STOX1, but is needed more investigation. Also, the oxidative stress has a main role, with the releasing of free oxygen and ONOO-, substances which make more intense the maternal dysfunction. The metabolism of lipids has a role, too. From the placenta, are also produced two anti-vascular proteins, sflt1 και Seng. sflt1 bound the factor VEGF, who is responsible for the angio-genesis. These factors can be used, in the future, as an instrument to the prognosis, in combination with uterine artery Doppler ultrasound. Because of the multifactorial pathogenesis of different preeclampsia phenotypes, prevention and prediction are still not possible and symptomatic clinical management should be mainly directed to prevent maternal mortality and morbidity. |
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Αναφορές – References
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1. Clark D.A.: The use and misuse of animal analog models of human pregnancy disorders. J. Reprod. Immunol. 103: 1-8 (2014) 2. Maynard S.E., Min J.Y., Merchan J., Lim K.H., Li J.,Mondal S., Libermann T.A., Morgan J.P., Sellke F.W., Stillman I.E., Epstein F.H., Sukhatme V.P., Karumanchi S.A.: J. Clin. Invest. 111(5): 649-658 (2003) 3. Roberts J.M., Hubel C.A.: The two stage model of preeclampsia: variations on the theme. Placenta 30(Suppl. A): S32-S37 (2009) 5. Wang W.Y., Barratt B.J., Clayton D.G., Todd J.A.: Genome-wide association studies: theoretical and practical concerns. Nat. Rev. Genet. 6: 109-118 (2005) 6. Moses E.K., Fitzpatrick E., Freed K.A., Dyer T.D., Forrest S., Elliott K., et al.: Objective prioritization of positional candidate genes at a quantitative trait locus for preeclampsia on 2q22. Mol. Hum. Reprod. 12: 505-512 (2006) 7. Roten L.T., Johnson M.P., Forsmo S., Fitzpatrick E., Dyer T.D., Brennecke S.P., et al., Association between the candidate susceptibility gene ACVR2A on chromosome 2q22 and pre-eclampsia in a large Norwegian population based study (the HUNT study). Eur. J. Hum. Genet. 17: 250-257 (2009) 8. Fitzpatrick E., Johnson M.P., Dyer T.D., Forrest S., Elliott K., Blangero J., Brennecke S.P., Moses E.K.: Genetic association of the activin A receptor gene (ACVR2A) and pre-eclampsia. Mol. Hum. Reprod. 15: 195-204 (2009) 9. Lokki A.I., Klemetti M M., Heino S., Hiltunen L., Heinonen S., Laivuori H.: Association of the rs1424954 polymorphism of the ACVR2A gene with the risk of preeclampsia is not replicated in a Finnish study population. BMC Res. Notes 4: 545 (2011) 10. Jones R.L., Salamonsen L.A., Findlay J.K.: Activin A promotes human endometrial stromal cell decidualization in vitro. J. Clin. Endocrinol. Metab. 87: 4001-4004 (2002) 11. Caniggia I., Lye S.J., Cross J.C.: Activin is a local regulator of human cytotrophoblast cell differentiation. Endocrinology 138: 3976-3986 (1997) 12. Giguère Y., Charland M., Bujold E., Bernard N., Grenier S., Rousseau F., Lafond J., Légaré F., Forest J.C.: Combining biochemical and ultrasonographic markers in predicting preeclampsia: a systematic review. Clin. Chem. 56: 361-375 (2010) 13. Kivinen K., Peterson H., Hiltunen L., Laivuori H., Heino S., Tiala I., et al., Evaluation of STOX1 as a preeclampsia candidate gene in a population-wide sample. Eur. J. Hum. Genet. 15: 494-497 (2007) 14. Buurma A.J., Turner R.J., Driessen J.H., Mooyaart A.L., Schoones J.W., Bruijn J.A., et al.: Genetic variants in preeclampsia: a meta-analysis. Hum. Reprod. Update 19: 289-303 (2013) 15. Tavana Z., Hosseinmirzaei S.: Comparison of maternal serum magnesium level in pre-eclampsia and normal pregnant women. Iran Red Crescent. Med. J. 15(12): e10394, 2013 doi: 10.5812/ircmj.10394. Epub 2013 Dec 5. 16. Nikolaides K.H., Brindra R., Tutzan O.M., et al.: A novel approach to first trimester screening for early preeclampsia compining PP-13 and Doppler ultrasound. Ultrasound Obstet. Gynecol. 27: 13-17 (2006) 17. Spencer K., Cowans M.J., Chefetz I.: First trimester maternal serum PP-13, PAPP-13 and second trimester uterine artery Doppler pulsatility index aw markers of preeclampsia. Ultrasound Obstet. Gynecol. 29: 128-134 (2007) 18. Huppertz B., Meiri H., Gizurarson S., Osol G., Sammar M.: Placental protein 13 (PP13): a new biological target shifting individualized risk assessment to personalized drug design combating pre-eclampsia. Hum. Reprod. Update 19: 391-405 2013) 19. Textoris J., Ivorra D., Ben Amara A., Sabatier F., Ménard J.P., Heckenroth H., Bretelle F., Mege J.L.: Evaluation of current and new biomarkers in severe preeclampsia: a microarray approach reveals the VSIG4 gene as a potential blood biomarker. PLoS One. 8(12): e82638.(2013)- Arngrímsson R., Sigurõardóttir S., Frigge M.L., Bjarnadóttir R. I., Jónsson T., Stefánsson H., et al.: A genome-wide scan reveals a maternal susceptibility locus for preeclampsia on chromosome 2p13. Hum. Mol. Genet. 8: 1799-1805 (1999) – Berends A.L., Bertoli-Avella A.M., de Groot C.J., van Duijn C.M., Oostra B.A., Steegers E.A.: STOX1 gene in preeclampsia and intrauterine growth restriction. BJOG 114: 1163-1167 (2007) – Chazara O., Xiong S., Moffett A.: Maternal KIR and fetal HLA-C: a fine balance. J. Leukoc. Biol. 90: 703-716 (2011) – Cindrova-Davies T., Spasic-Boskovic O., Jauniaux E., Charnock-Jones D.S., BurtonG.J.: Nuclear factor-kappa B, p38, and stress-activated protein kinase mitogen-activated protein kinase signaling pathways regulate proinflammatory cytokines and apoptosis in human placental explants in response to oxidative stress: effects of antioxidant vitamins. Am. J. Pathol. 170: 1511-1520 (2014) – Cui Y., Wang W., Dong N., Lou J., Srinivasan D. K., Cheng W., et al.: Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy. Nature 484(7393): 246-250 (2012) – Doridot L., Passet B., Méhats C., Rigourd V., Barbaux S., Ducat A., et al.: Preeclampsia-like symptoms induced in mice by fetoplacental expression of STOX1 are reversed by aspirin treatment. Hypertension 61: 662-668 (2013) – Duley L., The global impact of pre-eclampsia and eclampsia. Semin. Perinatol. 33: 130-137 (2009) – Fenstad M.H., Johnson M.P., Løset M., Mundal S.B., Roten L.T., Eide I.P., et al.: STOX2 but not STOX1 is differentially expressed in decidua from pre-eclamptic women: data from the Second Nord-Trondelag Health Study. Mol. Hum. Reprod. 16: 960-968 (2012) – Fitzpatrick E., Göring H.H., Liu H., Borg A., Forrest S., Cooper D.W., Brennecke S.P., Moses E.K: Fine mapping and SNP analysis of positional candidates at the preeclampsia susceptibility locus (PREG1) on chromosome 2. Hum. Biol. 76: 849-862 (2004) – Haram K., Svendsen E., Abildgaard U.: The HELLP syndrome: clinical issues and management. A Review. BMC Pregnancy Childbirth 26: 8 (2009) – Iglesias-Platas I., Monk D., Jebbink J., Buimer M., Boer K., van der Post J., et al.: STOX1 is not imprinted and is not likely to be involved in preeclampsia. Nat. Genet. 39: 279-280 (2007) – James J.L., Whitley G.S., Cartwright J.E.: Pre-eclampsia: fitting together the placental, immune and cardiovascular pieces. J. Pathol. 221: 363-378 (2010) – Janssens B., Goossens S., Staes K., Gilbert B., van Hengel J., Colpaert C., et al.: alphaT-catenin: a novel tissue-specific beta-catenin-binding protein mediating strong cell-cell adhesion. J. Cell. Sci. 114: 3175-3188 (2001) – Johnson M.P., Fitzpatrick E., Dyer T.D., Jowett J.B., Brennecke S.P., Blangero J., Moses E.K.: Identification of two novel quantitative trait loci for pre-eclampsia susceptibility on chromosomes 5q and 13q using a variance components-based linkage approach. Mol. Hum. Reprod. 13: 61-67 (2007) – Kanayama N., Takahashi K., Matsuura T., Sugimura M., Kobayashi T., Moniwa N., Nakayama K.: Deficiency in p57Kip2 expression induces preeclampsia-like symptoms in mice. Mol. Human Reprod. 8: 1129-1135 (2002) – Laasanen J., Hiltunen M., Romppanen E.L., Punnonen K., Mannermaa A., Heinonen S.: (2003).Microsatellite marker association at chromosome region 2p13 in Finnish patients with preeclampsia and obstetric cholestasis suggests a common risk locus. Eur. J. Hum. Genet. 11: 232-236 (2003) – Lachmeijer A.M., Arngrímsson R., Bastiaans E.J., Frigge M.L., Pals G., Sigurdardóttir S., et al., A genome-wide scan for preeclampsia in the Netherlands. Eur. J. Hum. Genet. 9: 758-764 (2001) – Laivuori H.: Genetic aspects of preeclampsia. Front. Biosci. 12: 2372-2382 (2007) – Laivuori H., Lahermo P., Ollikainen V., Widen E., Häivä-Mällinen L., Sundström H., et al.: Susceptibility loci for preeclampsia on chromosomes 2p25 and 9p13 in Finnish families. Am. J. Hum. Genet. 72: 168-177 (2003) – Long W., Shi Z., Fan S., Liu L., Lu Y., Guo X., Rong C., Cui X., Ding H.: Association of maternal KIR and fetal HLA-C genes with the risk of preeclampsia in Chinese Han population. Placenta pii: S 0143 – 221, 2014 – Moses E.K., Lade J.A., Guo G., Wilton A.N., Grehan M., Freed K., et al.: A genome scan in families from Australia and New Zealand confirms the presence of a maternal susceptibility locus for pre-eclampsia, on chromosome 2. Am. J. Hum. Genet. 67: 1581-1585 (2000) – Oudejans C.B., Mulders J., Lachmeijer A.M., van Dijk M., Könst A.A., Westerman B.A., et al.: The parent-of-origin effect of 10q22 in pre-eclamptic females coincides with two regions clustered for genes with down-regulated expression in androgenetic placentas. Mol. Hum. Reprod. 10: 589-598 (2004) – Rigourd V., Chauvet C., Chelbi S.T., Rebourcet R., Mondon F., Letourneur F., et al., STOX1 overexpression in choriocarcinoma cells mimics transcriptional alterations observed in preeclamptic placentas. PLoS One 3: 12, 2008 – Spencer K., Cowans M.J., Chefetz I.: First trimester maternal serum PP-13, PAPP-13 and second trimester uterine artery Doppler pulsatility index aw markers of preeclampsia. Ultrasound Obstet. Gynecol. 29: 128-134 (2007) – Steegers E.A., von Dadelszen P., Duvekot J.J., Pijnenborg R.: Pre-eclampsia. Lancet 376(9741): 631-644 (2010) – Treloar S.A., Cooper D.W., Brennecke S.P., Grehan M.M., Martin N.G.: An Australian twin study of the genetic basis of preeclampsia and eclampsia. Am. J. Obstet. Gynecol. 184: 374-381 (2001) – Tyberghein K., Goossens S., Haigh J.J., van Roy F, van Hengel J.: Tissue-wide overexpression of alpha-T-catenin results in aberrant trophoblast invasion but does not cause embryonic mortality in mice. Placenta 33: 554-560 (2012) – van Dijk M., Drewlo S., Oudejans C.B.: Differential methylation of STOX1 in human placenta. Epigenetics 5: 736-742 (2010) – van Dijk M., Mulders J., Poutsma A., Könst A.A., Lachmeijer A.M., Dekker G.A., et al.: Maternal segregation of the Dutch preeclampsia locus at 10q22 with a new member of the winged helix gene family. Nat. Genet. 37: 514-519 (2005) – van Dijk M., Thulluru H.K., Mulders J., Michel O.J., Poutsma A., Windhorst S., et al.: HELLP babies link a novel lincRNA to the trophoblast cell cycle. J. Clin. Invest. 122: 4003-4011 (2012) – van Dijk M., van Bezu J., Chim S.S., Lo Y.M., Blankenstein M.A., Oudejans C.B.: Reply to: STOX1 is not imprinted and is not likely to be involved in preeclampsia. Nat. Genet. 39: 280-281 (2007) – van Dijk M., van Bezu J., van Abel D., Dunk C., Blankenstein M.A., Oudejans C.B., et al.: The STOX1 genotype associated with pre-eclampsia leads to a reduction of trophoblast invasion by alpha-T-catenin upregulation. Hum. Mol. Genet. 19: 2658-2667 (2010) – Wallis A.B., Saftlas A.F., Hsia J., Atrash H.K.: Secular trends in the rates of preeclampsia, eclampsia and gestational hypertension. Am. J. Hypertens. 21: 521-526 (2008) |
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