Cosma G, Crofts F, Taioli E, Toniolo P, Garte S
Institute of Environmental Medicine, New York University Medical Center, New York 10987.
J Toxicol Environ Health. 1993 Oct-Nov;40(2-3):309-16. doi: 10.1080/15287399309531796.
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.
为了确定CYP1A1基因多态性的频率以及CYP1A1基因型与功能之间的关系，在一个种族多样化的人群中进行了人类CYP1A1基因型和酶活性的比较研究。限制性片段长度多态性分析显示，亚洲人变异型Msp1多态性的频率显著高于欧裔美国人，而非裔美国人的CYP1A1基因型频率更接近亚洲人。将Msp1位点的CYP1A1基因型与该基因第7外显子中的一个多态性位点进行比较，发现Msp1位点变异基因型的频率更高。通过乙氧基异吩恶唑酮O-脱乙基酶测定法测量淋巴细胞CYP1A1酶活性，结果显示，与野生型基因型个体相比，第7外显子变异基因型个体的诱导酶活性水平显著升高。这些结果表明CYP1A1基因型存在种族差异模式，并提示负责许多致癌多环芳烃代谢的细胞色素P-450蛋白的基因型与催化活性之间存在功能联系。
