Abstract:
:One of the major challenges in the near future is the identification of genes that affect the metabolism of different drugs. Large scale association studies that utilise single nucleotide polymorphisms (SNPs) have been considered a valuable tool for this purpose. CYP2D6, CYP2C19, CYP2C9, CYP3A4 and CYP1A2 were found to be involved in the majority of hepatically cleared drugs. To determine the allele frequencies of some SNPs that may have great potential value in forensic science, we screened 50 SNPs in these 5 CYP genes in Chinese Han people using an accurate, high-throughput, cost-effective method. Primers were designed using the MassARRAY Assay Design software. Genomic DNA was prepared from blood samples obtained from individuals of Chinese Han origin. Multiplex PCR was performed to amplify the relevant gene fragments, and the polymorphisms were analysed by allele-specific primer extension followed by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). A panel of genomic DNA samples previously genotyped by other methods were analysed simultaneously for quality control, and the results demonstrated that this assay was 100% accurate. A total of 17 of the analysed SNPs were polymorphic. Of these 17 SNPs, 8 (rs16947, rs28371725, rs1800754, rs4244285, rs4986893, rs12248560, rs3758580, rs2242480) had an allele frequency that was significantly different between this Chinese Han population and Caucasians (p<0.01). In addition, the frequencies of two of these SNPs (rs1800754, rs3758581) in our Chinese Han population differed significantly from the existing Chinese frequency data (p<0.01). The described method thus provides reliable results and enables the genotyping of up to thousands of samples by taking advantage of the high-throughput MALDI-TOF technology. The results herein are now included as a supplement to the P450 database.
journal_name
Forensic Sci Intjournal_title
Forensic science internationalauthors
Shi Y,Xiang P,Li L,Shen Mdoi
10.1016/j.forsciint.2010.10.004subject
Has Abstractpub_date
2011-04-15 00:00:00pages
183-7issue
1-3eissn
0379-0738issn
1872-6283pii
S0379-0738(10)00461-5journal_volume
207pub_type
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