Wedlund P J, Kimura S, Gonzalez F J, Nebert D W
Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD 20892.
Pharmacogenetics. 1994 Feb;4(1):21-6.
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.
之前对一个有15名成员的地中海东部血统的三代家族进行了研究，报道了细胞色素P1450（苯并[a]芘羟化酶）CYP1A1的诱导性与CYP1A1 3'-多态性（Msp I 1.9 kb等位基因）之间的关联（彼得森等人，《美国人类遗传学杂志》1991年；48:720 - 725）。在此，我们重新检测了这些相同个体的原始DNA（在某些情况下，还检测了新采集血液新制备的DNA），以评估CYP1A1诱导性与CYP1A1基因Msp I限制性片段长度多态性（RFLP）以及CYP1A1基因第462位密码子A→G多态性之间的关联。后一种核苷酸变化导致氨基酸改变（462Ile→Val），据称在日本人中，这会使CYP1A1酶活性和对苯并[a]芘的致突变性增加约两倍。在检测的这个三代家族的15名成员中，未观察到1462V基因型与Msp I 1.9 kb等位基因或CYP1A1诱导性表型之间存在绝对相关性。我们还发现Msp I 1.9 kb等位基因与CYP1A1诱导性表型之间不存在绝对相关性。
