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.