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

CASTAÑO GO; BURGUEÑO AL; FERNANDEZ GIANOTTI T; PIROLA CJ; SOOKOIAN S

ALIMENTARY PHARMACOLOGY & THERAPEUTICS.

WILEY-BLACKWELL PUBLISHING, INC

Año: 2010 vol. 31 p. 583 - 592

0269-2813

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: 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, 3 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 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.