Publication in refereed journal
香港中文大学研究人员 ( 现职)
| 左中教授 (药剂学院) |
全文
| 数位物件识别号 (DOI) http://dx.doi.org/10.2174/138920007782798199 |
引用次数
Web of Sciencehttp://aims.cuhk.edu.hk/converis/portal/Publication/15WOS source URL
其它资讯
摘要The pregnane X receptor (PXR/NR112) 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 NR112 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 I of NR112, 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 NR112 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 http://aims.cuhk.edu.hk/converis/portal/Publication/15 linkage disequilibriums were detected; and positive linkage disequilibriums were found between -2438 1A>C in exon I and -24113G>A in intron 1, and 252A>G in intron 2 and 275A>G in intron 2 (rho(2) = 1, p<0.00 I). A total of 42 haplotypes were inferred and the two most frequent haplotypes were H1 (TCAGGGGCCACC) and H2 (CCGAAAACTAAT) with a frequency of http://aims.cuhk.edu.hk/converis/portal/Publication/15-1%. The activity of the recombinants with alleles containing the -24622A>T 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 NR112 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 NR112 in various ethnic groups.
着者Wang XD, Li JL, Su QB, Deng XY, Lu Y, Chen J, Zhang JX, Zhao LZ, Zuo Z, Chan E, Chen X, Chowbay B, Xue CC, Huang M, Zhou SF
期刊名称Current Drug Metabolism
出版年份2007
月份12
日期1
卷号8
期次8
出版社BENTHAM SCIENCE PUBL LTD
页次778 - 786
国际标準期刊号1389-2002
电子国际标準期刊号1875-5453
语言英式英语
关键词Chinese; ethnicity; haplotype; pregnane X receptor (NR1I2); SNP
Web of Science 学科类别Biochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Pharmacology & Pharmacy; PHARMACOLOGY & PHARMACY
