Research Council in Health, Government of City of Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
Aliment Pharmacol Ther. 2010 Mar;31(5):583-92. doi: 10.1111/j.1365-2036.2009.04210.x. Epub 2009 Dec 3.
The xenobiotic nuclear pregnane X receptor is implicated in many physiological pathways and diseases, including bile acid detoxification and cholestasis. Aim To estimate the contribution of common gene variants of the xenobiotic receptor (pregnane X receptor, PXR) to genetic susceptibility to intrahepatic cholestasis of pregnancy.
A total of 101 intrahepatic cholestasis of pregnancy patients and 171 healthy pregnant women in the third trimester of their pregnancies were included. Four tag single nucleotide polymorphisms (SNPs) (rs12488820 C/T, rs2472671 C/T, rs2461823 A/G, and rs1054191 A/G) encompassing 36 kb in chromosome 3, with a minor allele frequency > or =0.10 and representing 33 polymorphic sites were genotyped. Besides these, three additional SNPs (rs3814057, rs6785049, and rs7643645) were included because they showed previous evidence of functionality.
Genotypic test for single SNPs showed that rs2461823 genotypes were significantly associated with intrahepatic cholestasis of pregnancy (P < 0.0069), OR per G allele: 1.44, 95% CI: 1.01-2.05, P < 0.042. The Cochran-Armitage test for trend and the allelic test showed a significant association with disease status (P < 0.04 and 0.03 respectively), G being the risk allele. A positive association between rs2461823 and ALT, AST, and bilirubin concentrations was observed. Neonate birth weight adjusted by the Capurro index was significantly associated with rs2461823 (P < 0.05); the proportion of the total variation attributed to rs2461823 genotypes was 7.8%.
Common PXR polymorphisms may contribute to the genetic susceptibility to intrahepatic cholestasis of pregnancy.
外源性核孕烷 X 受体（pregnane X receptor，PXR）参与多种生理途径和疾病，包括胆汁酸解毒和胆汁淤积。目的：评估外源性受体（PXR）常见基因变异与妊娠肝内胆汁淤积症（intrahepatic cholestasis of pregnancy，ICP）遗传易感性的关系。
纳入 101 例 ICP 患者和 171 例孕晚期健康孕妇。共检测包含 36 kb 染色体 3 上的 4 个标签单核苷酸多态性（single nucleotide polymorphisms，SNP）（rs12488820 C/T、rs2472671 C/T、rs2461823 A/G 和 rs1054191 A/G），其最小等位基因频率（minor allele frequency，MAF）≥0.10，代表 33 个多态性位点。此外，还包括 3 个先前有功能证据的 SNP（rs3814057、rs6785049 和 rs7643645）。
单 SNP 基因型检验显示，rs2461823 基因型与 ICP 显著相关（P < 0.0069），每个 G 等位基因的优势比（odds ratio，OR）为 1.44，95%可信区间（confidence interval，CI）为 1.01-2.05，P < 0.042。Cochran-Armitage 趋势检验和等位基因检验均显示与疾病状态显著相关（P < 0.04 和 0.03），G 为风险等位基因。rs2461823 与 ALT、AST 和胆红素浓度呈正相关。校正 Capurro 指数后的新生儿出生体重与 rs2461823 显著相关（P < 0.05）；rs2461823 基因型总变异的比例为 7.8%。
常见的 PXR 多态性可能与 ICP 的遗传易感性有关。
