Screening of Dihydropyrimidine Dehydrogenase Genetic Variants by Direct Sequencing in Different Ethnic Groups.
10.3346/jkms.2013.28.8.1129
- Author:
Joong Gon SHIN
1
;
Hyun Sub CHEONG
;
Jason Yongha KIM
;
Lyoung Hyo KIM
;
Chang Soo HAN
;
Ji On KIM
;
Hae Deun KIM
;
Young Hoon KIM
;
Myeon Woo CHUNG
;
Soon Young HAN
;
Hyoung Doo SHIN
Author Information
1. Department of Life Science, Sogang University, Seoul, Korea. hdshin@sogang.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Ethnic Gropus;
Pharmacogenetics;
Dihydropyrimidine Dehydrogenase;
Fluorouracil
- MeSH:
African Americans/genetics;
Alleles;
Amino Acids/metabolism;
Asian Continental Ancestry Group/genetics;
Dihydrouracil Dehydrogenase (NADP)/*genetics;
Ethnic Groups/*genetics;
European Continental Ancestry Group/genetics;
Fluorouracil/metabolism;
Gene Frequency;
Genotype;
Humans;
Polymorphism, Single Nucleotide;
Sequence Analysis, DNA
- From:Journal of Korean Medical Science
2013;28(8):1129-1133
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
