Translating DPYD genotype into DPD phenotype: using the DPYD gene activity score

被引：85

作者：

Henricks, Linda M. ^{[1
,2
]}

Lunenburg, Carin A. T. C. ^{[3
]}

Meulendijks, Didier ^{[1
,2
]}

Gelderblom, Hans ^{[3
]}

Cats, Annemieke ^{[4
]}

Swen, Jesse J. ^{[5
]}

Schellens, Jan H. M. ^{[1
,2
,6
]}

Guchelaar, Henk-Jan ^{[5
]}

机构：

[1] Netherlands Canc Inst, Dept Med Oncol, Div Clin Pharmacol, Amsterdam, Netherlands

[2] Netherlands Canc Inst, Dept Mol Pathol, Amsterdam, Netherlands

[3] Leiden Univ, Med Ctr, Dept Med Oncol, NL-2300 RC Leiden, Netherlands

[4] Netherlands Canc Inst, Dept Gastroenterol & Hepatol, Amsterdam, Netherlands

[5] Leiden Univ, Med Ctr, Dept Clin Pharm & Toxicol, NL-2300 RC Leiden, Netherlands

[6] Univ Utrecht, Fac Sci, Dept Pharmaceut Sci, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands

来源：

PHARMACOGENOMICS | 2015年 / 16卷 / 11期

关键词：

capecitabine; dihydropyrimidine dehydrogenase; DPYD; 5-fluorouracil; fluoropyrimidines; gene activity score; individualized medicine; pharmacogenomics; DIHYDROPYRIMIDINE DEHYDROGENASE GENE; SINGLE NUCLEOTIDE POLYMORPHISMS; COLORECTAL-CANCER PATIENTS; SPLICE DONOR SITE; IVS14+1G-GREATER-THAN-A MUTATION; 5-FLUOROURACIL TOXICITY; POINT MUTATION; DIHYDROURACIL/URACIL RATIO; FLUOROPYRIMIDINE TOXICITY; THYMIDYLATE-SYNTHASE;

D O I：

10.2217/pgs.15.70

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The dihydropyrimidine dehydrogenase enzyme (DPD, encoded by the gene DPYD) plays a key role in the metabolism of fluoropyrimidines. DPD deficiency occurs in 4-5% of the population and is associated with severe fluoropyrimidine-related toxicity. Several SNPs in DPYD have been described that lead to absent or reduced enzyme activity, including DPYD*2A, DPYD*13, c.2846A>T and c.1236G>A/haplotype B3. Since these SNPs differ in their effect on DPD enzyme activity, a differentiated dose adaption is recommended. We propose the gene activity score for translating DPYD genotype into phenotype, accounting for differences in functionality of SNPs. This method can be used to standardize individualized fluoropyrimidine dose adjustments, resulting in optimal safety and effectiveness.

引用

页码：1275 / 1284

页数：10

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