van Dijk Marie, Oudejans Cees
Molecular Biology Laboratory, Department of Clinical Chemistry, VU University Medical Center Amsterdam, Netherlands ; Institute for Cardiovascular Research VU, VU University Medical Center Amsterdam, Netherlands.
Front Genet. 2013 Sep 10;4:180. doi: 10.3389/fgene.2013.00180.
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 (ACVR2A, STOX1) and the HELLP-syndrome (LINC-HELLP) are discussed regarding their potential functions in the etiology of disease. Furthermore, susceptibility genes identified by candidate gene approaches (e.g., CORIN) 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 STOX1 gene and provide further evidence for the role of epigenetics in pre-eclampsia based on the cdkn1c 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.
本综述描述了目前关于胎盘源性妊娠相关疾病的遗传学和表观遗传学的知识。我们讨论了胎儿基因型决定母亲表型时对遗传连锁分析的影响。其次，讨论了全基因组连锁研究确定的与子痫前期（ACVR2A、STOX1）和HELLP综合征（LINC-HELLP）相关的基因在疾病病因学中的潜在功能。此外，还描述了通过候选基因方法（如CORIN）确定的易感基因。接下来，我们关注表观遗传学在疾病遗传中也发挥作用时所带来的额外挑战。我们讨论了包含STOX1基因的10q22染色体子痫前期连锁区域的母系传递，并基于子痫前期的cdkn1c小鼠模型为表观遗传学在子痫前期中的作用提供了进一步证据。最后，我们就如何阐明妊娠相关疾病的遗传学提出建议，特别是关于患者群体的明确定义、足够的患者数量，以及（表观）遗传数据在早期非侵入性生物标志物开发中的潜在用途。
