Nunoya K, Yokoi T, Takahashi Y, Kimura K, Kinoshita M, Kamataki T
Laboratory of Drug Metabolism, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, 060-0812, Japan.
J Biochem. 1999 Aug;126(2):402-7. doi: 10.1093/oxfordjournals.jbchem.a022464.
To clarify the molecular mechanisms involved in the generation of the CYP2A6 gene deletion (E-type variant), we analyzed the CYP2A7 gene, which is located in the 5'-flanking region of the CYP2A6 gene, from individuals with the E-type variant and compared it with the sequences of wild type CYP2A7 and CYP2A6 genes. The 3'-downstream sequence (up to 324 bp from the SacI site in exon 9) of the CYP2A7 gene of the E-type variant is identical to that of the wild CYP2A7 gene. However, the 3'-downstream sequence (starting from 325 bp from the SacI site in exon 9) of the CYP2A7 gene of the E-type variant is identical to that of the wild CYP2A6 gene, indicating that the 3'-downstream region of CYP2A7 and the 3'-downstream region of CYP2A6 linked directly eliminating the whole CYP2A6 gene. PCR analysis using primers specific to the CYP2A7 gene and the CYP2A6 and CYP2A7 genes confirmed that all DNA samples obtained from 7 individuals carrying the E-type variant possessed the same break points. These results indicate that the breakpoint of the CYP2A6 gene deletion lies in the 3'-downstream region of the CYP2A7 and CYP2A6 genes.
为阐明CYP2A6基因缺失（E型变体）产生过程中涉及的分子机制，我们分析了位于CYP2A6基因5'侧翼区域的CYP2A7基因，该分析针对具有E型变体的个体，并将其与野生型CYP2A7和CYP2A6基因的序列进行比较。E型变体的CYP2A7基因的3'下游序列（从外显子9中SacI位点起至324 bp）与野生型CYP2A7基因的相同。然而，E型变体的CYP2A7基因的3'下游序列（从外显子9中SacI位点的325 bp处开始）与野生型CYP2A6基因的相同，这表明CYP2A7的3'下游区域与CYP2A6的3'下游区域直接相连，从而消除了整个CYP2A6基因。使用针对CYP2A7基因以及CYP2A6和CYP2A7基因的特异性引物进行的PCR分析证实，从7名携带E型变体的个体获得的所有DNA样本都具有相同的断点。这些结果表明，CYP2A6基因缺失的断点位于CYP2A7和CYP2A6基因的3'下游区域。
