A genetic polymorphism in coumarin 7-hydroxylation: sequence of the human CYP2A genes and identification of variant CYP2A6 alleles.

摘要: A group of human cytochrome P450 genes encompassing the CYP2A, CYP2B, and CYP2F subfamilies were cloned assembled into a 350-kb contig localized on long arm chromosome 19. Three complete CYP2A - CYP2A6, CYP2A7, CYP2A13 plus two pseudogenes truncated after exon 5 identified sequenced. variant CYP2A6 allele that differed from corresponding CYP2A7 cDNAs previously sequenced was found designated CYP2A6{nu}2. Sequence differences in CY-P2A6{nu}2 gene are restricted to regions exons 3, 6, 8, which bear sequence relatedness with gene, located downstream centromeric CYP2A6{nu}2, suggesting recent gene-conversion events. The sequencing all allowed design PCR diagnostic test for normal allele, CYP2A6{nu}2 CYP2A6{nu}1 encodes an enzyme single inactivating amino acid change. These alleles individuals who deficient their ability metabolize probe drug coumarin. allelic frequencies significantly between Caucasian, Asian, African-American populations. studies establish existence new genetic polymorphism. 30 refs.,more » 4 figs., 2 tabs.« less