Kim Su-Ryang, Nakamura Takahiro, Saito Yoshiro, Sai Kimie, Nakajima Toshiharu, Saito Hirohisa, Shirao Kuniaki, Minami Hironobu, Ohtsu Atsushi, Yoshida Teruhiko, Saijo Nagahiro, Ozawa Shogo, Sawada Jun-ichi
Project team for Pharmacogenetics, National Institute of Health Sciences, Tokyo, Japan.
Drug Metab Pharmacokinet. 2003;18(5):327-32. doi: 10.2133/dmpk.18.327.
Twelve novel single nucleotide polymorphisms (SNPs) were found in the CES2 gene from 153 Japanese individuals, who were administered irinotecan or steroidal drugs. The detected SNPs were as follows:1) SNP, MPJ6_CS2001; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-CTGGAACAACTCG/CCTCCCCTCGGAA-3'. 2) SNP, MPJ6_CS2002; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-AACCACCACCGCT/CGATCCTAGCAGG-3'. 3) SNP, MPJ6_CS2003; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-AAATGTTTGTCAA/GGTGGATAAATGA-3'. 4) SNP, MPJ6_CS2004; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-CCTCCTATCGATC/GCCCCAGCGCGCT-3'. 5) SNP, MPJ6_CS2005; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-GCCAGTCCCATCC/TGGACCACACACA-3'. 6) SNP, MPJ6_CS2006; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-GCTGGGCAACCCG/AGGCTGAGCGGGG-3'. 7) SNP, MPJ6_CS2007; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-CAAGCACGCAACC/TGGCAACTGGGGC-3'. 8) SNP, MPJ6_CS2008; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-CATGGAGAGTGGC/TGTGGCCCTCCTG-3'. 9) SNP, MPJ6_CS2009; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-CCTGTTCTTGGCC/TAGGGCCTTGGGC-3'. 10) SNP, MPJ6_CS2010; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-CCCATCCCCAGCT/AACAGACTCTCTC-3'. 11) SNP, MPJ6_CS2011; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-TCCACCTGGGGTA/GGATGTTGCCTCC-3'. 12) SNP, MPJ6_CS2013; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-GGACTGGGGACCG/AAGGTCTCGGGGG-3'The frequencies were 0.029 for MPJ6_CS2004 and CS2013, 0.026 for MPJ6_CS2009, 0.013 for MPJ6_CS2001, 0.007 for MPJ6_CS2003, and 0.003 for the other 7 SNPs. Among these SNPs, MPJ6_CS2005 (100C>T) resulted in an amino acid alteration (R34W), and MPJ6_CS2007 (579C>T) and MPJ6_CS2008 (765C>T) were synonymous (T193T and G255G, respectively). Furthermore, MPJ6_CS2011 (IVS8-2A>G) resulted in variation at ther 3' splice acceptor site.
在153名接受伊立替康或甾体类药物治疗的日本个体的CES2基因中发现了12个新的单核苷酸多态性（SNP）。检测到的SNP如下：1）SNP，MPJ6_CS2001；基因名称，CES2；登录号，NT_010498.13；长度，25个碱基；5'-CTGGAACAACTCG/CCTCCCCTCGGAA-3'。2）SNP，MPJ6_CS2002；基因名称，CES2；登录号，NT_010498.13；长度，25个碱基；5'-AACCACCACCGCT/CGATCCTAGCAGG-3'。3）SNP，MPJ6_CS2003；基因名称，CES2；登录号，NT_010498.13；长度，25个碱基；5'-AAATGTTTGTCAA/GGTGGATAAATGA-3'。4）SNP，MPJ6_CS2004；基因名称，CES2；登录号，NT_010498.13；长度，25个碱基；5'-CCTCCTATCGATC/GCCCCAGCGCGCT-3'。5）SNP，MPJ6_CS2005；基因名称，CES2；登录号，NT_010498.13；长度，25个碱基；5'-GCCAGTCCCATCC/TGGACCACACACA-3'。6）SNP，MPJ6_CS2006；基因名称，CES2；登录号，NT_010498.13；长度，25个碱基；5'-GCTGGGCAACCCG/AGGCTGAGCGGGG-3'。7）SNP，MPJ6_CS2007；基因名称，CES2；登录号，NT_010498.13；长度，25个碱基；5'-CAAGCACGCAACC/TGGCAACTGGGGC-3'。8）SNP，MPJ6_CS2008；基因名称，CES2；登录号，NT_010498.13；长度，25个碱基；5'-CATGGAGAGTGGC/TGTGGCCCTCCTG-3'。9）SNP，MPJ6_CS2009；基因名称，CES2；登录号，NT_010498.13；长度，25个碱基；5'-CCTGTTCTTGGCC/TAGGGCCTTGGGC-3'。10）SNP，MPJ6_CS2010；基因名称，CES2；登录号，NT_010498.13；长度，25个碱基；5'-CCCATCCCCAGCT/AACAGACTCTCTC-3'。11）SNP，MPJ6_CS2011；基因名称，CES2；登录号，NT_010498.13；长度，25个碱基；5'-TCCACCTGGGGTA/GGATGTTGCCTCC-3'。12）SNP，MPJ6_CS2013；基因名称，CES2；登录号，NT_010498.13；长度，25个碱基；5'-GGACTGGGGACCG/AAGGTCTCGGGGG-3'。MPJ6_CS2004和CS2013的频率为0.029，MPJ6_CS2009的频率为0.026，MPJ6_CS2001的频率为0.013，MPJ6_CS2003的频率为0.007，其他7个SNP的频率为0.003。在这些SNP中，MPJ6_CS2005（100C>T）导致氨基酸改变（R34W），MPJ6_CS2007（579C>T）和MPJ6_CS2008（765C>T）是同义突变（分别为T193T和G255G）。此外，MPJ6_CS2011（IVS8-2A>G）导致3'剪接受体位点发生变异。
