Please use this identifier to cite or link to this item: https://doi.org/10.2174/138920007782798199
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dc.titleA pharmacogenetic study of pregnane X receptor (NR112) in Han Chinese
dc.contributor.authorWang, X.-D.
dc.contributor.authorLi, J.-L.
dc.contributor.authorSu, Q.-B.
dc.contributor.authorDeng, X.-Y.
dc.contributor.authorLu, Y.
dc.contributor.authorChen, J.
dc.contributor.authorZhang, J.-X.
dc.contributor.authorZhao, L.-Z.
dc.contributor.authorZuo, Z.
dc.contributor.authorChan, E.
dc.contributor.authorChen, X.
dc.contributor.authorChowbay, B.
dc.contributor.authorXue, C.C.
dc.contributor.authorHuang, M.
dc.contributor.authorZhou, S.-F.
dc.date.accessioned2014-10-29T02:02:23Z
dc.date.available2014-10-29T02:02:23Z
dc.date.issued2007-12
dc.identifier.citationWang, X.-D., Li, J.-L., Su, Q.-B., Deng, X.-Y., Lu, Y., Chen, J., Zhang, J.-X., Zhao, L.-Z., Zuo, Z., Chan, E., Chen, X., Chowbay, B., Xue, C.C., Huang, M., Zhou, S.-F. (2007-12). A pharmacogenetic study of pregnane X receptor (NR112) in Han Chinese. Current Drug Metabolism 8 (8) : 778-786. ScholarBank@NUS Repository. https://doi.org/10.2174/138920007782798199
dc.identifier.issn13892002
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/106603
dc.description.abstractThe pregnane X receptor (PXR/NR1I2) gene is a critical transcriptional regulator of a number of important drug metabolizing enzymes and transporters. This study was undertaken to determine the frequencies of single nucleotide polymorphisms. (SNPs) and haplotypes and to detect yet unknown SNPs in the NR1I2 gene in 210 unrelated healthy Han Chinese in comparison with other ethnic groups. We also characterized the functional impact of two SNPs, -24622A>T in the 5′-untranslated region and -24446C>A in exon 1 of NR1I2, by constructing three recombinants and monitoring promoter activity using the dual luciferase reporter gene assay. Genomic DNA was isolated from peripheral leukocytes and subjected to polymerase chain reaction (PCR) amplification, followed by direct DNA sequencing: Sixteen SNPs in NR1I2 with frequencies of 0.3-90.3% were found in Han Chinese, two of which (-25439A>G in the 5′-untranslated region and 7637C>T in intron 5) are previously unknown. The mutant allelic frequencies varied from 0.3% to 90.3%. Most of the detected SNPs were located in introns. A total of 15 linkage disequilibriums were detected; and positive linkage disequilibriums were found between -24381A>C in exon 1 and -24113G>A in intron 1, and 252A>G in intron 2 and 275A>G in intron 2 (p2 = 1, PT in the 5′-untranslated region or -24446C>A in exon 1 was 30-40% higher than that in the wild-type (reference genotype). These results indicate that there are marked ethnic differences in the frequency between Han Chinese and other ethnic groups and that alleles with -24622A>T in the 5′-untranslated region and - 24446C>A in exon 1 of the NR1I2 gene result in an increased activity compared to the wild-type. Further studies are warranted to explore the clinical and toxicological impact of SNPs and haplotypes of NR1I2 in various ethnic groups. © 2007 Bentham Science Publishers Ltd.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.2174/138920007782798199
dc.sourceScopus
dc.subjectChinese
dc.subjectEthnicity
dc.subjectHaplotype
dc.subjectPregnane X receptor (NR 112)
dc.subjectSNP
dc.typeReview
dc.contributor.departmentPHARMACY
dc.description.doi10.2174/138920007782798199
dc.description.sourcetitleCurrent Drug Metabolism
dc.description.volume8
dc.description.issue8
dc.description.page778-786
dc.description.codenCDMUB
dc.identifier.isiut000251208700004
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