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目的:探讨胎盘OATP1A2和OATP1B3的表达水平及OATP1B3基因多态性与妊娠期肝内胆汁淤积症(ICP)的关系。方法:收集42例ICP胎盘和42例正常妊娠胎盘标本及母体静脉血,RT-q PCR和Western blot法分析OATP1A2和OATP1B3的mRNA及蛋白水平,测序法分析OATP1B3 c.334T>G和c.699G>A多态性位点基因型。结果:ICP胎盘中OATP1A2和OATP1B3的mRNA及蛋白表达水平均显著低于正常妊娠组(P<0.05)。ICP组和正常妊娠组中,OATP1B3 c.334C>T多态性纯合突变频率分别为50.0%和47.6%(P>0.05),c.699G>A多态性纯合突变频率分别为54.8%和45.2%(P>0.05);两组的两种多态性的突变等位基因频率比较,差异均无统计学意义(70.2%vs 70.2%和73.8%vs 67.9%,P>0.05)。ICP组OATP1B3不同基因型对其mRNA及蛋白的表达无显著影响(P>0.05)。结论:ICP胎盘中OATP1A2和OATP1B3表达下调可能与ICP高胆汁酸的发生有关,而OATP1B3 c.334T>G和c.699G>A多态性不影响OATP1B3表达。
Objective: To investigate the expression of OATP1A2 and OATP1B3 in placenta and the relationship between OATP1B3 gene polymorphism and intrahepatic cholestasis of pregnancy (ICP). Methods: The mRNA and protein levels of OATP1A2 and OATP1B3 were detected by RT-q PCR and Western blot in 42 cases of ICP placenta and 42 cases of placenta accreta and maternal venous blood respectively. The sequence of OATP1B3 c.334T> G and c.699G > A polymorphic locus genotypes. Results: The mRNA and protein expressions of OATP1A2 and OATP1B3 in ICP placenta were significantly lower than those in normal pregnancy (P <0.05). In ICP group and normal pregnancy group, the frequency of homozygous mutation of c.334C> T polymorphism in OATP1B3 was 50.0% and 47.6% (P> 0.05), and the frequency of homozygous mutation in c.699G> A polymorphism was 54.8% And 45.2% respectively (P> 0.05). There was no significant difference in allele frequency between the two groups (70.2% vs 70.2% and 73.8% vs 67.9%, P> 0.05). The different genotypes of OATP1B3 in ICP group had no significant effect on the mRNA and protein expression (P> 0.05). Conclusion: The downregulation of OATP1A2 and OATP1B3 in ICP placenta may be related to the occurrence of ICP hyperbolic acid, while the OATP1B3 c.334T> G and c.699G> A polymorphisms do not affect OATP1B3 expression.