Catteau A, Douriez E, Beaune P, Poisson N, Bonaiti-Pellié C, Laurent P
Unité de Recherche d'Epidémiologie Génétique (U155 INSERM), Château de Longchamp, Bois de Boulogne, Paris, France.
Pharmacogenetics. 1995 Apr;5(2):110-9. doi: 10.1097/00008571-199504000-00008.
CYP1A1 is a cytochrome P450 which is inducible by polycyclic aromatic hydrocarbons (PAH). This induction is mediated via the Ahr locus which encodes the cytosolic Aryl hydrocarbon receptor. The induced activity of CYP1A1 can be measured in vitro by the ethoxyresorufin-O-deethylase (EROD) activity in lymphocytes after induction by benz(a)anthracene (B(a)A). Our purpose was to determine, using this assay, the genetic polymorphism of CYP1A1 induction. With this aim, a population and family study was undertaken. Using the statistical SKUMIX method, a bimodal distribution (two peaks) of the induced EROD activity among 102 unrelated individuals was obtained. We were unable to discriminate three classes of CYP1A1 induction phenotype since a trimodal distribution did not significantly improve the fit to the data (chi 2(1) = 0.37, p > 0.9). Segregation analysis performed on 57 nuclear families gave evidence of a major gene effect together with a polygenic component. The frequency of the high induction allele is equal to 0.11 with dominance on the low induction allele. This is an accordance with two distributions, with individuals showing low and high CYP1A1 induction phenotypes in proportions of 89% and 21% respectively. However, some degree of overlap between the two distributions prevented a clear genotype classification on the basis of the phenotype measured with the EROD assay. Further analyses should not be made with a dichotomized phenotype (low and high inducers) but should use quantitative measurements.
细胞色素P450 1A1（CYP1A1）是一种可被多环芳烃（PAH）诱导的细胞色素P450。这种诱导作用是通过编码胞质芳烃受体的芳烃受体（Ahr）基因座介导的。CYP1A1的诱导活性可通过苯并(a)蒽（B(a)A）诱导后淋巴细胞中的乙氧基异吩恶唑酮 - O - 脱乙基酶（EROD）活性在体外进行测量。我们的目的是使用该检测方法确定CYP1A1诱导的基因多态性。为此，我们进行了一项群体和家系研究。使用统计SKUMIX方法，在102名无亲缘关系的个体中获得了诱导的EROD活性的双峰分布（两个峰值）。由于三峰分布并不能显著改善对数据的拟合度（卡方(1)=0.37，p>0.9），我们无法区分三类CYP1A1诱导表型。对57个核心家系进行的分离分析表明存在一个主基因效应以及一个多基因成分。高诱导等位基因的频率等于0.11，对低诱导等位基因具有显性作用。这与两种分布一致，个体表现出低和高CYP1A1诱导表型的比例分别为89%和21%。然而，两种分布之间存在一定程度的重叠，使得基于EROD检测所测表型进行明确的基因型分类变得困难。进一步的分析不应使用二分法表型（低诱导剂和高诱导剂），而应使用定量测量。
