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

CASTAÑO G.,; BURGUEÑO A.; FERNÁNDEZ GIANOTTI T.; PIROLA CJ.; SOOKOIAN S.

ALIMENTARY PHARMACOLOGY & THERAPEUTICS.

WILEY-BLACKWELL PUBLISHING, INC

Año: 2010 vol. 31 p. 583 - 592

0269-2813

SUMMARY 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 (ICP). Methods A total of 101 ICP 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 ‡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 ICP (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 ICP. Aliment Pharmacol Ther