当前位置： SCI文献检索 > ALIMENTARY PHARMACOLOGY & THERAPEUTICS期刊下所有文献 > The influence of common gene variants of the xenobiotic receptor (PXR) in genetic susceptibility to intrahepatic cholestasis of pregnancy.

The influence of common gene variants of the xenobiotic receptor (PXR) in genetic susceptibility to intrahepatic cholestasis of pregnancy.

Abstract：

BACKGROUND: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. METHODS: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. RESULTS: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%. CONCLUSION:Common PXR polymorphisms may contribute to the genetic susceptibility to intrahepatic cholestasis of pregnancy.

journal_name

Aliment Pharmacol Ther

journal_title

Alimentary pharmacology & therapeutics

authors

Castaño G,Burgueño A,Fernández Gianotti T,Pirola CJ,Sookoian S

doi

10.1111/j.1365-2036.2009.04210.x

subject

Has Abstract

pub_date

2010-03-01 00:00:00

pages

583-92

issue

5

eissn

0269-2813

issn

1365-2036

pii

APT4210

journal_volume

31

pub_type

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