RELATIONSHIP BETWEEN GENOTYPE AND FUNCTION OF THE HUMAN CYP1A1-GENE

A comparative study of human CYP1A1 genotypes and enzymatic activity w as performed in a racially diverse population in order to determine fr equencies of CYP1A1 genetic polymorphisms and the relationship between CYP1A1 genotype and function. Restriction fragment length polymorphis m analyses revealed significantly higher frequencies of a variant Msp1 polymorphism in Asians versus European-Americans, while African-Ameri can CYP1A1 genotypic frequencies more closely approximated those of As ians. Comparison of CYP1A1 genotypes at the Msp1 locus to a polymorphi c site in exon 7 of the gene revealed a higher frequency of variant ge notypes at the MSP1 site. Measurement of lymphocyte CYP1A1 enzyme acti vity by the ethoxyresorufin O-deethylase assay revealed significantly elevated levels of inducible enzyme activity among variant exon 7 geno types when compared to wild-type genotypic individuals. These results demonstrate racially distinct patterns of CYP1A1 genotypes, and sugges t a functional link between genotype and catalytic activity of the cyt ochrome P-450 protein responsible for the metabolism of many carcinoge nic polycyclic aromatic hydrocarbons.