title: 1462V mutation in the human CYP1A1 gene: lack of correlation with either the Msp I 1.9 kb (M2) allele or CYP1A1 inducibility in a three-generation family of east Mediterranean descent.
abstract: A 15-member three-generation family of Eastern Mediterranean descent was previously studied, and an association between CYP1A1 (cytochrome P1450, benzo[a]pyrene hydroxylase) inducibility and a CYP1A1 3'-polymorphism (the Msp I 1.9 kb allele) was reported (Petersen et al., Am J Hum Genet 1991:48, 720-725). Here we have re-examined the original DNA (and in some cases, newly prepared DNA from freshly drawn blood) from these same individuals, in order to assess the association between CYP1A1 inducibility and both the CYP1A1 gene Msp I RFLP polymorphism and the CYP1A1 gene A-->G polymorphism at codon 462. This latter nucleotide change results in an altered amino acid (462Ile-->Val), which is purported to increase CYP1A1 enzyme activity and mutagenicity towards benzo[a]pyrene about two-fold among Japanese. Among the 15 members of this three-generation family examined, no absolute correlation was observed between the 1462V genotype and either the Msp I 1.9 kb allele or the CYP1A1 inducibility phenotype. We also found no absolute correlation between the Msp I 1.9 kb allele and the CYP1A1 inducibility phenotype.
authors.affiliation: Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD 20892.
authors.forename: P J
authors.initials: PJ
authors.lastname: Wedlund
authors.forename: S
authors.initials: S
authors.lastname: Kimura
authors.forename: F J
authors.initials: FJ
authors.lastname: Gonzalez
authors.forename: D W
authors.initials: DW
authors.lastname: Nebert
mesh_terms: D000483:Alleles; D001579:Benzopyrene Hydroxylase / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D019003:Deoxyribonuclease HpaII; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D004790:Enzyme Induction; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015894:Genome, Human; D006801:Humans; D008297:Male; D008522:Mediterranean Sea; D009154:Mutation; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D003577:Cytochrome P-450 Enzyme System; D001579:Benzopyrene Hydroxylase; D019003:Deoxyribonuclease HpaII; D015252:Deoxyribonucleases, Type II Site-Specific