AUTHOR=Oudejans Cees , Van Dijk Marie 

TITLE=(Epi)genetics of pregnancy-associated diseases

JOURNAL=Frontiers in Genetics

VOLUME=4

YEAR=2013

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2013.00180

DOI=10.3389/fgene.2013.00180

ISSN=1664-8021

ABSTRACT=<p>This review describes the current knowledge regarding genetics and epigenetics of pregnancy-associated diseases with placental origin. We discuss the effect on genetic linkage analyses when the fetal genotype determines the maternal phenotype. Secondly, the genes identified by genome-wide linkage studies to be associated with pre-eclampsia (<italic>ACVR2A</italic>, <italic>STOX1</italic>) and the HELLP-syndrome (<italic>LINC-HELLP</italic>) are discussed regarding their potential functions in the etiology of disease. Furthermore, susceptibility genes identified by candidate gene approaches (e.g., <italic>CORIN</italic>) are described. Next, we focus on the additional challenges that come when epigenetics also play a role in disease inheritance. We discuss the maternal transmission of the chromosome 10q22 pre-eclampsia linkage region containing the <italic>STOX1</italic> gene and provide further evidence for the role of epigenetics in pre-eclampsia based on the <italic>cdkn1c</italic> mouse model of pre-eclampsia. Finally, we provide recommendations to unravel the genetics of pregnancy-associated diseases, specifically regarding clear definitions of patient groups and sufficient patient numbers, and the potential usefulness of (epi)genetic data in early non-invasive biomarker development.</p>