Insitute of Medical Sciences, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
Placenta. 2010 May;31(5):351-7. doi: 10.1016/j.placenta.2010.02.010. Epub 2010 Mar 27.
Recent studies have illustrated the importance of placental drug transport proteins, such as P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) in limiting fetal exposure to drugs and toxins. Moreover, increasing evidence supports a role for Pgp and BCRP in the normal development and physiological function of the placenta. Several single nucleotide polymorphisms (SNPs) in the genes encoding Pgp and BCRP have been described and are associated with altered protein expression, transporter activity, and clinical outcome in studies focusing on tissues other than the placenta. This review aims to summarize current research regarding the association between these polymorphisms and expression and function in the placenta. The influence of these genotypes on fetal drug exposure and altered placental physiology or development is also presented. To date, evidence suggests that SNPs in both ABCB1 and ABCG1 can alter expression of their respective protein; however, the functional significance of these polymorphisms is less clear. An understanding of this genotype-phenotype relationship will allow for prediction of susceptible or favorable genotypes in order to personalize medication choices to minimize fetal exposure to teratogens, or to maximize pharmacological therapy to the fetus.
最近的研究表明，胎盘药物转运蛋白（如 P-糖蛋白（Pgp）和乳腺癌耐药蛋白（BCRP））在限制胎儿暴露于药物和毒素方面非常重要。此外，越来越多的证据表明 Pgp 和 BCRP 在胎盘的正常发育和生理功能中发挥作用。编码 Pgp 和 BCRP 的基因中的几个单核苷酸多态性（SNP）已被描述，并与除胎盘以外的组织中关注的蛋白质表达、转运体活性和临床结果改变相关。这篇综述旨在总结目前关于这些多态性与胎盘表达和功能之间关系的研究。还介绍了这些基因型对胎儿药物暴露和胎盘生理或发育改变的影响。迄今为止，有证据表明，ABCB1 和 ABCG1 中的 SNP 可以改变其各自蛋白的表达；然而，这些多态性的功能意义尚不清楚。了解这种基因型-表型关系将有助于预测易感或有利的基因型，以便根据胎儿暴露于致畸物的风险程度来个性化选择药物，或最大程度地提高胎儿的药物治疗效果。
