Department of Life Science, Sogang University, Seoul, Korea.
J Korean Med Sci. 2013 Aug;28(8):1129-33. doi: 10.3346/jkms.2013.28.8.1129. Epub 2013 Jul 31.
Dihydropyrimidine dehydrogenase (DPYD) is an enzyme that regulates the rate-limiting step in pyrimidine metabolism, especially catabolism of fluorouracil, a chemotherapeutic agent for cancer. In order to determine the genetic distribution of DPYD, we directly sequenced 288 subjects from five ethnic groups (96 Koreans, 48 Japanese, 48 Han Chinese, 48 African Americans, and 48 European Americans). As a result, 56 polymorphisms were observed, including 6 core polymorphisms and 18 novel polymorphisms. Allele frequencies were nearly the same across the Asian populations, Korean, Han Chinese and Japanese, whereas several SNPs showed different genetic distributions between Asians and other ethnic populations (African American and European American). Additional in silico analysis was performed to predict the function of novel SNPs. One nonsynonymous SNP (+199381A > G, Asn151Asp) was predicted to change its polarity of amino acid (Asn, neutral to Asp, negative). These findings would be valuable for further research, including pharmacogenetic and drug responses studies.
二氢嘧啶脱氢酶（DPYD）是一种调节嘧啶代谢限速步骤的酶，特别是氟尿嘧啶（一种用于癌症治疗的化疗药物）的分解代谢。为了确定 DPYD 的遗传分布，我们直接对来自五个种族（96 名韩国人、48 名日本人、48 名汉族人、48 名非裔美国人、48 名欧洲裔美国人）的 288 名个体进行了测序。结果观察到 56 种多态性，包括 6 种核心多态性和 18 种新的多态性。等位基因频率在亚洲人群（韩国人、汉族人和日本人）中几乎相同，而一些单核苷酸多态性（SNP）在亚洲人和其他种族人群（非裔美国人和欧洲裔美国人）之间表现出不同的遗传分布。还进行了额外的计算机分析来预测新 SNP 的功能。一个非同义 SNP（+199381A > G，Asn151Asp）被预测会改变其氨基酸的极性（Asn，中性变为 Asp，负性）。这些发现对于进一步的研究很有价值，包括药物遗传学和药物反应研究。
