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致畸物遗传易感性:最新进展。

Genetic susceptibility to teratogens: state of the art.

机构信息

Teratology Information Service, Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy.

出版信息

Reprod Toxicol. 2012 Sep;34(2):186-91. doi: 10.1016/j.reprotox.2012.05.004. Epub 2012 Jun 1.

Abstract

There is evidence that the susceptibility to the teratogenic effect of drugs within human populations varies extremely from one individual to another, even after identical exposures. One of the factors that may explain these interindividual differences is the genetic makeup in the pharmacokinetics and pharmacodynamics of the respective drugs. In fact, both maternal and embryonic/fetal genotypes can affect placental transport, absorption, metabolism, distribution and receptor binding of an agent, influencing its teratogenicity. We have reviewed the literature and commented on the reported correlations between genetic factors and drug-induced birth defects. There is still a clear lack of knowledge regarding this issue and the available data are often conflicting. However, the identification of specific polymorphisms associated with predisposition to teratogenesis may allow in the future the development of personalized non-teratogenic therapies for pregnant women.

摘要

有证据表明,即使在相同暴露的情况下,人群对药物致畸作用的易感性也在个体之间存在极大差异。这些个体差异的原因之一可能是药物代谢动力学和药效学的遗传构成。事实上,母体和胚胎/胎儿的基因型都会影响药物在胎盘的转运、吸收、代谢、分布和受体结合,从而影响其致畸性。我们回顾了文献,并对遗传因素与药物引起的出生缺陷之间的报告相关性进行了评论。关于这个问题,我们的认识仍然明显不足,而且现有数据往往相互矛盾。然而,鉴定与致畸易感性相关的特定多态性可能有助于未来为孕妇制定个性化的非致畸治疗方法。

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