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.
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 pregnancypatients 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.
Authors: Jann Yuan Wang; Ching Hui Tsai; Yungling Leo Lee; Li Na Lee; Chia Lin Hsu; Hsiu Ching Chang; Jong Ming Chen; Cheng An Hsu; Chong Jen Yu; Pan Chyr Yang Journal: Medicine (Baltimore) Date: 2015-06 Impact factor: 1.889
Authors: Yuanyuan Zhang; Fei Li; Yao Wang; Aaron Pitre; Zhong-Ze Fang; Matthew W Frank; Christopher Calabrese; Kristopher W Krausz; Geoffrey Neale; Sharon Frase; Peter Vogel; Charles O Rock; Frank J Gonzalez; John D Schuetz Journal: Nat Commun Date: 2015-09-29 Impact factor: 14.919
Authors: Romina Cabrerizo; Gustavo O Castaño; Adriana L Burgueño; Tomas Fernández Gianotti; María Mora Gonzalez Lopez Ledesma; Diego Flichman; Carlos J Pirola; Silvia Sookoian Journal: PLoS One Date: 2014-01-31 Impact factor: 3.240