title: Relationship between genotype and function of the human CYP1A1 gene.
abstract: A comparative study of human CYP1A1 genotypes and enzymatic activity was performed in a racially diverse population in order to determine frequencies of CYP1A1 genetic polymorphisms and the relationship between CYP1A1 genotype and function. Restriction fragment length polymorphism analyses revealed significantly higher frequencies of a variant Msp1 polymorphism in Asians versus European-Americans, while African-American CYP1A1 genotypic frequencies more closely approximated those of Asians. Comparison of CYP1A1 genotypes at the Msp1 locus to a polymorphic site in exon 7 of the gene revealed a higher frequency of variant genotypes at the Msp1 site. Measurement of lymphocyte CYP1A1 enzyme activity by the ethoxyresorufin O-deethylase assay revealed significantly elevated levels of inducible enzyme activity among variant exon 7 genotypes when compared to wild-type genotypic individuals. These results demonstrate racially distinct patterns of CYP1A1 genotypes, and suggest a functional link between genotype and catalytic activity of the cytochrome P-450 protein responsible for the metabolism of many carcinogenic polycyclic aromatic hydrocarbons.
authors.affiliation: Institute of Environmental Medicine, New York University Medical Center, New York 10987.
authors.forename: G
authors.initials: G
authors.lastname: Cosma
authors.forename: F
authors.initials: F
authors.lastname: Crofts
authors.forename: E
authors.initials: E
authors.lastname: Taioli
authors.forename: P
authors.initials: P
authors.lastname: Toniolo
authors.forename: S
authors.initials: S
authors.lastname: Garte
mesh_terms: D001483:Base Sequence; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000378:metabolism; D010375:Pedigree; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1