Project Team for Pharmacogenetics, National Institute of Health Sciences, Tokyo 158-8501, Japan.
Drug Metab Pharmacokinet. 2009;24(6):553-6. doi: 10.2133/dmpk.24.553.
Cytidine deaminase, encoded by the CDA gene, catalyzes anti-cancer drugs gemcitabine and ara-C into their respective inactive metabolites. In CDA, two functionally significant non-synonymous polymorphisms, 79A>C (Lys27Gln) and 208G>A (Ala70Thr), have been found and their minor allele frequencies (MAFs) were reported in Japanese and Chinese patients and a relatively small numbers of healthy volunteers in Caucasians and Africans. In this study, we determined the MAFs of both polymorphisms in 200 healthy volunteers of Koreans, along with 206 Japanese, 200 Chinese-Americans, 150 Caucasian-Americans and 150 African-Americans to reveal ethnic differences. MAFs of 79A>C (Lys27Gln) were 0.153 in Koreans and 0.327 in Caucasian-Americans, 0.204 in Japanese, 0.155 in Chinese-Americans and 0.087 in African-Americans. MAFs of 208G>A (Ala70Thr) were 0.005 in Koreans and 0.022 in Japanese and the minor allele was not detected in Chinese-Americans, Caucasian-Americans or African-Americans. Thus possibly, MAF of 208G>A in Japanese is likely to be somewhat higher than in Koreans and Chinese-Americans. These data would provide fundamental and useful information for pharmacogenetic studies on cytidine deaminase-catalyzing drugs.
胞苷脱氨酶由 CDA 基因编码，可将抗癌药物吉西他滨和阿糖胞苷转化为各自的无活性代谢物。在 CDA 中，已经发现了两个具有重要功能的非同义多态性，79A>C（Lys27Gln）和 208G>A（Ala70Thr），其在日本和中国患者以及相对较少的白种人和非洲裔健康志愿者中的小等位基因频率（MAF）已有报道。在这项研究中，我们确定了这两个多态性在 200 名韩国健康志愿者、206 名日本、200 名美籍华裔、150 名白种人和 150 名非裔美国人中的 MAF，以揭示种族差异。79A>C（Lys27Gln）的 MAF 在韩国人为 0.153，在白种美国人为 0.327，在日本人为 0.204，在美籍华裔中为 0.155，在非裔美国人为 0.087。208G>A（Ala70Thr）的 MAF 在韩国人为 0.005，在日本人为 0.022，美籍华裔、白种美国人和非裔美国人中未检测到小等位基因。因此，208G>A 在日本的 MAF 可能略高于韩国和美籍华裔。这些数据将为胞苷脱氨酶催化药物的药物遗传学研究提供基础和有用的信息。
