Nejatizadeh Azim, Stobdan Tsering, Malhotra Neena, Pasha M A Qadar
Functional Genomics Unit, Institute of Genomics and Integrative Biology, Delhi, 110 007, India.
Biochem Genet. 2008 Aug;46(7-8):451-79. doi: 10.1007/s10528-008-9163-9. Epub 2008 Apr 24.
Pre-eclampsia, a life-threatening disease during pregnancy, is a leading cause of global maternal mortality. Although there is substantial evidence of a genetic background, the complexity of the processes involved and nature of the maternal-fetal phenomenon do not make the search for the causative genes easy. Recent retrospective studies on the subject suggest the heritable allelic variations, particularly the utero-placental renin-angiotensin system with defective placental vascular development, could become the cornerstone for the genetics of pre-eclampsia and hence might well be associated with such defective development. Moreover, the role of immune mechanisms (immune maladaptation) deserves not to be ignored. Large-scale studies entailing genomewide scanning, sib-pair linkage analysis, and family-based association studies with appropriate power to detect genes with a lower relative risk are necessary to understand the puzzle of the disease. Moreover, recently, the importance of epigenetic features and the effect of imprinted genes related to trophoblast growth as well as fetal development on hypertension in pregnancy have been highlighted. All these possibilities are intuitively attractive and are supported by some circumstantial evidence. Although the consistent tenor of a series of papers instill some confidence, we need meticulously designed larger-scale investigations including large numbers of affected women and their babies to provide the analytic stringency essential to study the polygenic multifactorial basis of pre-eclampsia.
子痫前期是妊娠期一种危及生命的疾病，是全球孕产妇死亡的主要原因。尽管有大量证据表明该病存在遗传背景，但由于所涉及过程的复杂性以及母胎现象的性质，寻找致病基因并非易事。近期关于该主题的回顾性研究表明，可遗传的等位基因变异，特别是胎盘血管发育缺陷的子宫 - 胎盘肾素 - 血管紧张素系统，可能成为子痫前期遗传学的基石，因此很可能与这种发育缺陷有关。此外，免疫机制（免疫适应不良）的作用也不容忽视。需要进行大规模研究，包括全基因组扫描、同胞对连锁分析以及基于家系的关联研究，且要有足够的能力检测相对风险较低的基因，以解开该疾病之谜。此外，最近，表观遗传特征的重要性以及与滋养层生长和胎儿发育相关的印记基因对妊娠期高血压的影响也受到了关注。所有这些可能性从直观上看都很有吸引力，并且有一些间接证据支持。尽管一系列论文的一致主旨让人产生了一些信心，但我们需要精心设计的更大规模调查，包括大量患病女性及其婴儿，以提供研究子痫前期多基因多因素基础所必需的分析严谨性。
