The genetics of pre-eclampsia: a feto-placental or maternal problem?
The genetics of pre-eclampsia: a feto-placental or maternal problem?
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DOI：
10.1034/j.1399-0004.2003.00127.x
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发表时间：
2003-08-01
影响因子：
3.5
通讯作者：
Cross, JC
中科院分区：
文献类型：
--
作者：
Cross, JC
先兆子痫是妊娠期一种潜在威胁生命的疾病，会导致高血压和蛋白尿。它影响着十五分之一的孕妇，但是，尽管进行了大量的研究工作，这种疾病的原因仍然是个谜。由于先兆子痫只发生在怀孕期间，其症状在分娩后消失，因此来自胎盘的因素被认为是相关因素。胎盘的作用可能是产生“异常”因子，引发广泛的炎症和血管收缩。或者，由于胎盘通常有助于孕妇对妊娠的心血管适应，可能是正常的胎盘功能在先兆子痫中失效，或者是母亲对高血压、血管和/或肾脏疾病的易感性阻碍了对它们的适当正常反应。母体和胎儿基因对疾病发病的潜在贡献使人类疾病的基因分析变得复杂。最近的研究已经确定了转基因和突变小鼠的品系，它们具有先兆子痫样疾病的显著特征-妊娠期高血压、蛋白尿和肾脏损害(肾小球硬化)。对三种不同的小鼠模型的比较表明，先兆子痫至少可以由三种独立的机制启动：先前存在的因怀孕而加剧的交界性母体高血压(BPH/5小鼠品系)，因胎盘肾素过度产生而导致母体循环中血管收缩素II水平升高(肾素/血管紧张素原转基因小鼠)，以及胎盘病理(p57(Kip2)突变小鼠)。这些发现表明，先兆子痫的发病机制不能用单一的机制来解释。因此，将人类疾病分成不同的亚型可能是识别遗传风险因素的关键第一步。
Pre-eclampsia is a potentially life-threatening disease of women during pregnancy leading to hypertension and proteinuria. It affects 1 in 15 pregnancies but, despite intense research efforts, the cause of the disease remains mysterious. Because pre-eclampsia only occurs during pregnancy and its symptoms resolve after delivery, factors from the placenta are thought to be involved. The role of the placenta could be production of 'abnormal' factors that initiate widespread inflammation and vaso-constriction. Alternatively, because the placenta normally contributes to maternal cardiovascular adaptations of pregnancy, it may be that normal placental functions fail in pre-eclampsia or that susceptibilities in the mother to hypertensive, vascular and/or renal disease prevent the appropriate normal responses to them. The potential contributions of both maternal and fetal genes to the onset of the disease have complicated the genetic analysis of the disease in humans. Recent studies have identified strains of transgenic and mutant mice that develop the hallmark features of pre-eclampsia-like disease - gestational hypertension, proteinuria and kidney lesions (glomerulosclerosis). Comparison of three different mouse models suggests that pre-eclampsia can be initiated by at least three independent mechanisms: pre-existing borderline maternal hypertension that is exacerbated by pregnancy (BPH/5 strain of mice), elevated levels of the vasoconstrictor angiotensin II in the maternal circulation by placental over-production of renin (renin/angiotensinogen transgenic mice), and placental pathology (p57 (Kip2) mutant mice). These findings imply that the pathogenesis of pre-eclampsia cannot be explained by a single mechanism. Therefore, segregation of the human disease into different subtypes may be a key first step in identifying genetic risk factors.