Genotyping NUDT15 can predict the dose reduction of 6-MP for children with acute lymphoblastic leukemia especially at a preschool age
The pharmacokinetics among children has been altered dynamically. The difference between children and adults is caused by immaturity in things such as metabolic enzymes and transport proteins. The periods when these alterations happen vary from a few days to some years after birth. We hypothesized t...
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| Veröffentlicht in: | Journal of human genetics 2016-09, Vol.61 (9), p.797-801 |
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| creator | Suzuki, Hisato Fukushima, Hiroko Suzuki, Ryoko Hosaka, Sho Yamaki, Yuni Kobayashi, Chie Sakai, Aiko Imagawa, Kazuo Iwabuchi, Atsushi Yoshimi, Ai Nakao, Tomohei Kato, Keisuke Tsuchida, Masahiro Kiyokawa, Nobutaka Koike, Kazutoshi Noguchi, Emiko Fukushima, Takashi Sumazaki, Ryo |
| description | The pharmacokinetics among children has been altered dynamically. The difference between children and adults is caused by immaturity in things such as metabolic enzymes and transport proteins. The periods when these alterations happen vary from a few days to some years after birth. We hypothesized that the effect of gene polymorphisms associated with the dose of medicine could be influenced by age. In this study, we analyzed 51 patients with childhood acute lymphoblastic leukemia (ALL) retrospectively. We examined the associations between the polymorphism in NUDT15 and clinical data, especially the dose of 6-mercaptopurine (6-MP). Ten of the patients were heterozygous for the variant allele in NUDT15. In patients under 7 years old with NUDT15 variant allele, the average administered dose of 6-MP was lower than that for the patients homozygous for the wild-type allele (P=0.04). Genotyping of NUDT15 could be a beneficial to estimate the tolerated dose of 6-MP for patients with childhood ALL, especially at a preschool age in Japan. Furthermore, the analysis with stratification by age might be useful in pharmacogenomics among children. |
| doi_str_mv | 10.1038/jhg.2016.55 |
| format | Article |
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The difference between children and adults is caused by immaturity in things such as metabolic enzymes and transport proteins. The periods when these alterations happen vary from a few days to some years after birth. We hypothesized that the effect of gene polymorphisms associated with the dose of medicine could be influenced by age. In this study, we analyzed 51 patients with childhood acute lymphoblastic leukemia (ALL) retrospectively. We examined the associations between the polymorphism in NUDT15 and clinical data, especially the dose of 6-mercaptopurine (6-MP). Ten of the patients were heterozygous for the variant allele in NUDT15. In patients under 7 years old with NUDT15 variant allele, the average administered dose of 6-MP was lower than that for the patients homozygous for the wild-type allele (P=0.04). Genotyping of NUDT15 could be a beneficial to estimate the tolerated dose of 6-MP for patients with childhood ALL, especially at a preschool age in Japan. Furthermore, the analysis with stratification by age might be useful in pharmacogenomics among children.</description><identifier>ISSN: 1434-5161</identifier><identifier>EISSN: 1435-232X</identifier><identifier>DOI: 10.1038/jhg.2016.55</identifier><identifier>PMID: 27193222</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Adolescent ; Age Factors ; Alleles ; Antimetabolites, Antineoplastic - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Child ; Child, Preschool ; Female ; Gene Frequency ; Genetic Association Studies ; Genotype ; Humans ; Infant ; Male ; Mercaptopurine - administration & dosage ; Methyltransferases - genetics ; Pharmacogenetics ; Polymorphism, Genetic ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Pyrophosphatases - genetics</subject><ispartof>Journal of human genetics, 2016-09, Vol.61 (9), p.797-801</ispartof><rights>Copyright Nature Publishing Group Sep 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c495t-cfd6aadd52b5942bf4579828171fa11869ac44c836bdde088e585fbeb0a6653c3</citedby><cites>FETCH-LOGICAL-c495t-cfd6aadd52b5942bf4579828171fa11869ac44c836bdde088e585fbeb0a6653c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27193222$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Suzuki, Hisato</creatorcontrib><creatorcontrib>Fukushima, Hiroko</creatorcontrib><creatorcontrib>Suzuki, Ryoko</creatorcontrib><creatorcontrib>Hosaka, Sho</creatorcontrib><creatorcontrib>Yamaki, Yuni</creatorcontrib><creatorcontrib>Kobayashi, Chie</creatorcontrib><creatorcontrib>Sakai, Aiko</creatorcontrib><creatorcontrib>Imagawa, Kazuo</creatorcontrib><creatorcontrib>Iwabuchi, Atsushi</creatorcontrib><creatorcontrib>Yoshimi, Ai</creatorcontrib><creatorcontrib>Nakao, Tomohei</creatorcontrib><creatorcontrib>Kato, Keisuke</creatorcontrib><creatorcontrib>Tsuchida, Masahiro</creatorcontrib><creatorcontrib>Kiyokawa, Nobutaka</creatorcontrib><creatorcontrib>Koike, Kazutoshi</creatorcontrib><creatorcontrib>Noguchi, Emiko</creatorcontrib><creatorcontrib>Fukushima, Takashi</creatorcontrib><creatorcontrib>Sumazaki, Ryo</creatorcontrib><title>Genotyping NUDT15 can predict the dose reduction of 6-MP for children with acute lymphoblastic leukemia especially at a preschool age</title><title>Journal of human genetics</title><addtitle>J Hum Genet</addtitle><description>The pharmacokinetics among children has been altered dynamically. The difference between children and adults is caused by immaturity in things such as metabolic enzymes and transport proteins. The periods when these alterations happen vary from a few days to some years after birth. We hypothesized that the effect of gene polymorphisms associated with the dose of medicine could be influenced by age. In this study, we analyzed 51 patients with childhood acute lymphoblastic leukemia (ALL) retrospectively. We examined the associations between the polymorphism in NUDT15 and clinical data, especially the dose of 6-mercaptopurine (6-MP). Ten of the patients were heterozygous for the variant allele in NUDT15. In patients under 7 years old with NUDT15 variant allele, the average administered dose of 6-MP was lower than that for the patients homozygous for the wild-type allele (P=0.04). Genotyping of NUDT15 could be a beneficial to estimate the tolerated dose of 6-MP for patients with childhood ALL, especially at a preschool age in Japan. Furthermore, the analysis with stratification by age might be useful in pharmacogenomics among children.</description><subject>Adolescent</subject><subject>Age Factors</subject><subject>Alleles</subject><subject>Antimetabolites, Antineoplastic - administration & dosage</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>Genetic Association Studies</subject><subject>Genotype</subject><subject>Humans</subject><subject>Infant</subject><subject>Male</subject><subject>Mercaptopurine - administration & dosage</subject><subject>Methyltransferases - genetics</subject><subject>Pharmacogenetics</subject><subject>Polymorphism, Genetic</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics</subject><subject>Pyrophosphatases - genetics</subject><issn>1434-5161</issn><issn>1435-232X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpd0U1v1DAQBuAIUdEPOHFHI3FBqrL1R5w4R1SgILWFQytxixx7svHixKntCO0P4H_jpYUDJ4-lRzOjeYviNSUbSri82I3bDSO03gjxrDihFRcl4-z78z91VQpa0-PiNMYdIYSzhr0ojllDW84YOyl-XeHs036x8xZu7z_cUQFazbAENFYnSCOC8REh_1edrJ_BD1CXN99g8AH0aJ0JOMNPm0ZQek0Ibj8to--dislqcLj-wMkqwLigtsq5PagE6jAh6tF7B2qLL4ujQbmIr57es-L-08e7y8_l9derL5fvr0tdtSKVejC1UsYI1ou2Yv1QiaaVTNKGDopSWbdKV5WWvO6NQSIlCimGHnui6lpwzc-Kd499l-AfVoypm2zU6Jya0a-xo5I1LaGSskzf_kd3fg1z3i6rKt8uX5xmdf6odPAxBhy6JdhJhX1HSXdIp8vpdAfbCZH1m6eeaz-h-Wf_xsF_A5WRiwQ</recordid><startdate>20160901</startdate><enddate>20160901</enddate><creator>Suzuki, Hisato</creator><creator>Fukushima, Hiroko</creator><creator>Suzuki, Ryoko</creator><creator>Hosaka, Sho</creator><creator>Yamaki, Yuni</creator><creator>Kobayashi, Chie</creator><creator>Sakai, Aiko</creator><creator>Imagawa, Kazuo</creator><creator>Iwabuchi, Atsushi</creator><creator>Yoshimi, Ai</creator><creator>Nakao, Tomohei</creator><creator>Kato, Keisuke</creator><creator>Tsuchida, Masahiro</creator><creator>Kiyokawa, Nobutaka</creator><creator>Koike, Kazutoshi</creator><creator>Noguchi, Emiko</creator><creator>Fukushima, Takashi</creator><creator>Sumazaki, Ryo</creator><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope></search><sort><creationdate>20160901</creationdate><title>Genotyping NUDT15 can predict the dose reduction of 6-MP for children with acute lymphoblastic leukemia especially at a preschool age</title><author>Suzuki, Hisato ; Fukushima, Hiroko ; Suzuki, Ryoko ; Hosaka, Sho ; Yamaki, Yuni ; Kobayashi, Chie ; Sakai, Aiko ; Imagawa, Kazuo ; Iwabuchi, Atsushi ; Yoshimi, Ai ; Nakao, Tomohei ; Kato, Keisuke ; Tsuchida, Masahiro ; Kiyokawa, Nobutaka ; Koike, Kazutoshi ; Noguchi, Emiko ; Fukushima, Takashi ; Sumazaki, Ryo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c495t-cfd6aadd52b5942bf4579828171fa11869ac44c836bdde088e585fbeb0a6653c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adolescent</topic><topic>Age Factors</topic><topic>Alleles</topic><topic>Antimetabolites, Antineoplastic - 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The difference between children and adults is caused by immaturity in things such as metabolic enzymes and transport proteins. The periods when these alterations happen vary from a few days to some years after birth. We hypothesized that the effect of gene polymorphisms associated with the dose of medicine could be influenced by age. In this study, we analyzed 51 patients with childhood acute lymphoblastic leukemia (ALL) retrospectively. We examined the associations between the polymorphism in NUDT15 and clinical data, especially the dose of 6-mercaptopurine (6-MP). Ten of the patients were heterozygous for the variant allele in NUDT15. In patients under 7 years old with NUDT15 variant allele, the average administered dose of 6-MP was lower than that for the patients homozygous for the wild-type allele (P=0.04). Genotyping of NUDT15 could be a beneficial to estimate the tolerated dose of 6-MP for patients with childhood ALL, especially at a preschool age in Japan. Furthermore, the analysis with stratification by age might be useful in pharmacogenomics among children.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>27193222</pmid><doi>10.1038/jhg.2016.55</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Age Factors Alleles Antimetabolites, Antineoplastic - administration & dosage Antineoplastic Combined Chemotherapy Protocols - therapeutic use Child Child, Preschool Female Gene Frequency Genetic Association Studies Genotype Humans Infant Male Mercaptopurine - administration & dosage Methyltransferases - genetics Pharmacogenetics Polymorphism, Genetic Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics Pyrophosphatases - genetics |
| title | Genotyping NUDT15 can predict the dose reduction of 6-MP for children with acute lymphoblastic leukemia especially at a preschool age |
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