DNA methylation biomarkers for predicting pregnancy complications

Tina Bianco-Motto, Carlos Marcelino Rodríguez López, Shalem Leemaqz, Sam Buckberry, Dylan McCullough, Zimin Zhuang, Gus Dekker, Michael Wilkinson, Claire Roberts

Allbwn ymchwil: Cyfraniad at gynhadleddCrynodebadolygiad gan gymheiriaid


Preeclampsia (PE), preterm birth (PTB), small for gestational age (SGA), and gestational diabetes mellitus (GDM) afflict 1 in 4 of first pregnancies and can be life threatening to the mother and/or baby. Currently, there are no reliable biomarkers in clinical practice that discriminate which women are likely to have a complicated pregnancy. This is particularly important in first pregnancies where there is no previous pregnancy history to inform the clinician of the woman’s likely risk of a complicated pregnancy. The SCOPE (SCreening fOr Pregnancy Endpoints) interna- tional consortium of pregnancy research has assembled a biobank and detailed clinical and lifestyle database for nearly 6,000 women pregnant for the first time. In Adelaide, 1169 women were recruited prospectively with detailed clinical and lifestyle information, biological samples from mother, baby and father, as well as the known outcome of the pregnancy. Of the 1169 Adelaide SCOPE women 861 had uncomplicated pregnancies, 93 developed PE, 95 delivered SGA babies, 69 delivered preterm and 51 had GDM. To identify biomarkers for predicting pregnancy complica- tions, DNA was extracted from maternal buffy coat samples at 15 weeks’ gestation. Since the mechanisms by which environmental factors alter gene expression are thought to be epigenetic, and the most characterised epigenetic mechanism is DNA methylation, we investigated whether epigenetic biomarkers could predict pregnancy complications, either alone or in combination with clinical characteristics and genetic infor- mation (SNPs). Our preliminary data from 8 PE, 8 PTB and 8 uncompli- cated term pregnancies suggests that analysis of DNA methylation could generate reliable diagnostic markers to predict pregnancy outcome, us- ing a methodology known as methylation-sensitive genotyping-by- sequencing. Currently we are assessing more than 400 samples from women with the 4 common pregnancy complications and uncomplicated pregnancies to validate DNA methylation changes that can be used for screening maternal blood samples for pregnancy complication pre- diction.
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Dynodwyr Gwrthrych Digidol (DOIs)
StatwsCyhoeddwyd - 2015

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