Oyama T, Mitsudomi T, Kawamoto T, Ogami A, Osaki T, Kodama Y, Yasumoto K
Department of Surgery II, University of Occupational and Environmental Health, Kitakyushu, Japan.
Int Arch Occup Environ Health. 1995;67(4):253-6. doi: 10.1007/BF00409407.
Isoleucine (Ile)-valine (Val) polymorphism, which is caused by a point mutation from A to G in exon 7, is reported to be associated with an elevated risk of lung cancer among Japanese. Because CYP1A1 catalyzes bioactivation of environmental procarcinogens, such as benzo[a]pyrene, it is very important to study the clinical meaning of Ile-Val polymorphism using an epidemiological study. In an epidemiological study, easy, economical, rapid and reliable identification of the CYP1A1 genotype is necessary. The present study shows that the new method, designed restriction fragment length polymorphism (designed RFLP), can detect Ile-Val polymorphism of CYP1A1. The Ile-Val polymorphism detected using this new method was consistent with that found by the allele-specific PCR amplifications (ASA) method in six cases tested. This new method detected Ile-Val polymorphism of CYP1A1 using 240 healthy Japanese who lived in the northern Kyusyu region. The frequency of the genotypes was as follows: Ile/Ile 159 (66.2%); Ile/Val, 65 (27.1%); Val/Val, 16 (6.7%). The frequency of the Ile gene was 0.798 and that of the Val gene, 0.202. There was no difference in Ile-Val polymorphism based on sex or age. Racial differences influenced the distribution of this polymorphism, but Japanese regional differences did not. Since this new method, designed RFLP, is rapid, reliable and suitable for large-scale screening of polymorphisms, it may be used routinely to detect Ile-Val polymorphism of CYP1A1. Furthermore, it will help to evaluate the relationship between CYP1A1 polymorphism and individual sensitivity to xenobiotics that may affect the incidence of lung cancer.
异亮氨酸（Ile）-缬氨酸（Val）多态性是由外显子7中A到G的点突变引起的，据报道在日本人中与肺癌风险升高有关。由于细胞色素P450 1A1（CYP1A1）催化环境前致癌物如苯并[a]芘的生物活化，因此通过流行病学研究来探讨Ile-Val多态性的临床意义非常重要。在流行病学研究中，需要一种简便、经济、快速且可靠的方法来鉴定CYP1A1基因型。本研究表明，新设计的限制性片段长度多态性方法（设计RFLP）能够检测CYP1A1的Ile-Val多态性。在6例检测病例中，用这种新方法检测到的Ile-Val多态性与等位基因特异性PCR扩增（ASA）方法检测到的结果一致。本研究使用新方法检测了居住在九州北部地区的240名健康日本人的CYP1A1的Ile-Val多态性。基因型频率如下：Ile/Ile 159例（66.2%）；Ile/Val 65例（27.1%）；Val/Val 16例（6.7%）。Ile基因频率为0.798，Val基因频率为0.202。Ile-Val多态性在性别或年龄上没有差异。种族差异影响这种多态性的分布，但日本地区差异不影响。由于这种新的设计RFLP方法快速、可靠且适用于多态性的大规模筛查，它可常规用于检测CYP1A1的Ile-Val多态性。此外，它将有助于评估CYP1A1多态性与个体对外源化合物敏感性之间的关系，而这种敏感性可能影响肺癌的发病率。
