J Korean Med Sci.  2013 Aug;28(8):1129-1133. 10.3346/jkms.2013.28.8.1129.

Screening of Dihydropyrimidine Dehydrogenase Genetic Variants by Direct Sequencing in Different Ethnic Groups

• Shin JG
• Cheong HS
• Kim JY
• Kim LH
• Han CS
• Kim JO
• Kim HD
• Kim YH
• Chung MW
• Han SY
• Shin HD

• KMID: 1793015
• DOI: http://doi.org/10.3346/jkms.2013.28.8.1129

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.

Keyword

Ethnic Gropus; Pharmacogenetics; Dihydropyrimidine Dehydrogenase; Fluorouracil

MeSH Terms

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
Amino Acids
Dihydrouracil Dehydrogenase (NADP)
Fluorouracil

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