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

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...

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Autores principales: Shin, Joong-Gon, Cheong, Hyun Sub, Kim, Jason Yongha, Kim, Lyoung Hyo, Han, Chang Soo, Kim, Ji On, Kim, Hae Deun, Kim, Young Hoon, Chung, Myeon Woo, Han, Soon Young, Shin, Hyoung Doo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Academy of Medical Sciences 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744698/
https://www.ncbi.nlm.nih.gov/pubmed/23960437
http://dx.doi.org/10.3346/jkms.2013.28.8.1129
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author Shin, Joong-Gon
Cheong, Hyun Sub
Kim, Jason Yongha
Kim, Lyoung Hyo
Han, Chang Soo
Kim, Ji On
Kim, Hae Deun
Kim, Young Hoon
Chung, Myeon Woo
Han, Soon Young
Shin, Hyoung Doo
author_facet Shin, Joong-Gon
Cheong, Hyun Sub
Kim, Jason Yongha
Kim, Lyoung Hyo
Han, Chang Soo
Kim, Ji On
Kim, Hae Deun
Kim, Young Hoon
Chung, Myeon Woo
Han, Soon Young
Shin, Hyoung Doo
author_sort Shin, Joong-Gon
collection PubMed
description 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.
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spelling pubmed-37446982013-08-19 Screening of Dihydropyrimidine Dehydrogenase Genetic Variants by Direct Sequencing in Different Ethnic Groups Shin, Joong-Gon Cheong, Hyun Sub Kim, Jason Yongha Kim, Lyoung Hyo Han, Chang Soo Kim, Ji On Kim, Hae Deun Kim, Young Hoon Chung, Myeon Woo Han, Soon Young Shin, Hyoung Doo J Korean Med Sci Original Article 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. The Korean Academy of Medical Sciences 2013-08 2013-07-31 /pmc/articles/PMC3744698/ /pubmed/23960437 http://dx.doi.org/10.3346/jkms.2013.28.8.1129 Text en © 2013 The Korean Academy of Medical Sciences. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Shin, Joong-Gon
Cheong, Hyun Sub
Kim, Jason Yongha
Kim, Lyoung Hyo
Han, Chang Soo
Kim, Ji On
Kim, Hae Deun
Kim, Young Hoon
Chung, Myeon Woo
Han, Soon Young
Shin, Hyoung Doo
Screening of Dihydropyrimidine Dehydrogenase Genetic Variants by Direct Sequencing in Different Ethnic Groups
title Screening of Dihydropyrimidine Dehydrogenase Genetic Variants by Direct Sequencing in Different Ethnic Groups
title_full Screening of Dihydropyrimidine Dehydrogenase Genetic Variants by Direct Sequencing in Different Ethnic Groups
title_fullStr Screening of Dihydropyrimidine Dehydrogenase Genetic Variants by Direct Sequencing in Different Ethnic Groups
title_full_unstemmed Screening of Dihydropyrimidine Dehydrogenase Genetic Variants by Direct Sequencing in Different Ethnic Groups
title_short Screening of Dihydropyrimidine Dehydrogenase Genetic Variants by Direct Sequencing in Different Ethnic Groups
title_sort screening of dihydropyrimidine dehydrogenase genetic variants by direct sequencing in different ethnic groups
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744698/
https://www.ncbi.nlm.nih.gov/pubmed/23960437
http://dx.doi.org/10.3346/jkms.2013.28.8.1129
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