SNP Communication
Eleven Novel Single Nucleotide Polymorphisms in the NRH2 (PXR) Gene, Pour of which Induce Non-synonymous Amino Acid Alterations

https://doi.org/10.2133/dmpk.17.561Get rights and content

Summary:

Eleven novel single nucleotide polymorphisms (SNPs) were found in the NR1I2 (PXR/SXR) gene from 205 Japanese subjects. The detected SNPs were as follows:

  • 1)

    SNP, MPJ6_1I2001; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5′-TTTCTACCTCTAC/TTATTGAAAGGGC-3′

  • 2)

    SNP, MPJ6_1I2004; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5′-AGGCCCAAATGTG/AAGTGATGCATAG-3′

  • 3)

    SNP, MPJ6_1I2007; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5′-TGCCAGGCCTGCC/TGCCTGCGCAAGT-3′

  • 4)

    SNP, MPJ6_1I2008; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5′-GAGTGAGCAGTGG/CGCGCGCGGGCGG-3′

  • 5)

    SNP, MPJ6_1I2010; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5′-CAGAGGAGCAGCG/AGATGATGATCAG-3′

  • 6)

    SNP, MPJ6_1I2011; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5′-CTGGAAGTGGCCA/GGGAGGTTCAAAG-3′

  • 7)

    SNP, MPJ6_1I2013; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5′-TCTTCCTCTCGCC/TCCCAACTTCTGG-3′

  • 8)

    SNP, MPJ6_1I2017; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5′-ATTGAATGCAATC/TGGCCCCAGCCTG-3′

  • 9)

    SNP, MPJ6_1I2018; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5′-GGTGAGCACAGCA/GGGGGGTGAGGAC-3′

  • 10)

    SNP, MPJ6_H2019; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5′-GAGCTCCGCAGCA/GTCAATGCTCAGC-3′

  • 11)

    SNP, MPJ6_1I2021; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5′-GGTGACACCTCCG/AAGAGGCAGCCAG-3′.

The frequencies were 0.0293 for MPJ6_1I2021, 0.0073 for MPJ6_1I2011, and 0.0024 for the other 9 SNPs. All SNPs were found as heterozygous. Among these SNPs, MPJ6_1I2007, MPJ6_1I2010, MPJ6_1I2017 and MPJ6_1I2019 induce non-synonymous amino acid alterations (R98C, R148Q, R381W and I403V, respectively, in PAR1).

References (8)

  • G. Bertilsson et al.

    Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction

    Proc. Natl. Acad. Sci. USA

    (1998)
  • J.M. Lehmann et al.

    The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions

    J. Clin. Invest.

    (1998)
  • B. Blumberg et al.

    SXR, a novel steroid and xenobiotic-sensing nuclear receptor

    Genes Dev.

    (1998)
  • B. Goodwin et al.

    Regulation of CYP3A gene transcription by the pregnane X receptor

    Annu. Rev. Pharmacol. Toxicol.

    (2002)
There are more references available in the full text version of this article.

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    2017, Clinics and Research in Hepatology and Gastroenterology
    Citation Excerpt :

    It was reported that aberrant NR1I2 transcriptional activity was associated with the development of IBD, and the NR1I2 protein might be a novel target for IBD therapy [11,42–44]. Certain host NR1I2 genetic variants might take part in the regulation of the expression of target genes such as cytochrome P-450 monooxygenase 3A4 (CYP3A4) through affecting the secondary structure of the NR1I2 protein and the binding affinities for antagonistic ligands [15,45–47]. Hence, although no genetic correlations between NR1I2 variants and IBD risk were observed, we cannot rule out the potential roles of NR1I2 polymorphisms in the susceptibility to IBD.

  • Tryptophan 299 is a conserved residue of human pregnane X receptor critical for the functional consequence of ligand binding

    2016, Biochemical Pharmacology
    Citation Excerpt :

    These PXR protein variants may play a role in CYP3A4 expression and may be involved in altered sensitivities to carcinogens or atypical responses to drugs [37]. Interestingly, some of the previously identified naturally occurring variants (V140M, R148Q, D163G, R381W, A370T and I403V) are located within or close to the LBD of PXR [37–40]. However, no naturally occurring mutation of W299 has been reported.

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On October 11 2002, these SNPs were not found in “A database of Japanese Single Nucleotide Polymorphisms (http://snp.ims.u-tokyo.ac.jp/)” and “dbSNP in the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/SNP/)”, or “The Human Gene Mutation Database (http://archive.uwcm.ac.uk/uwcm/mg/hgmd0.html)”. This study was supported in part by the Program for the Promotion of Fundamental Studies in Health Sciences (MPJ-2, 3, 5 and 6) of the Organization for Pharmaceutical Safety and Research (OPSR) of Japan.

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