title: Screening of dihydropyrimidine dehydrogenase genetic variants by direct sequencing in different ethnic groups.
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.
authors: Department of Life Science, Sogang University, Seoul, Korea.
authors: Joong-Gon
authors: JG
authors: Shin
authors: Hyun Sub
authors: HS
authors: Cheong
authors: Jason Yongha
authors: JY
authors: Kim
authors: Lyoung Hyo
authors: LH
authors: Kim
authors: Chang Soo
authors: CS
authors: Han
authors: Ji On
authors: JO
authors: Kim
authors: Hae Deun
authors: HD
authors: Kim
authors: Young Hoon
authors: YH
authors: Kim
authors: Myeon Woo
authors: MW
authors: Chung
authors: Soon Young
authors: SY
authors: Han
authors: Hyoung Doo
authors: HD
authors: Shin
mesh_terms: D001741:Black or African American / Q000235:genetics; D000483:Alleles; D000596:Amino Acids / Q000378:metabolism; D044466:Asian People / Q000235:genetics; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005472:Fluorouracil / Q000378:metabolism; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics
chemical_list: D000596:Amino Acids; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil
keywords: Dihydropyrimidine Dehydrogenase; Ethnic Gropus; Fluorouracil; Pharmacogenetics
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