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

Linda M. Henricks; Carin A T C Lunenburg; Didier Meulendijks; Hans Gelderblom; Annemieke Cats; Jesse J. Swen; Jan H M Schellens; Henk Jan Guchelaar

doi:10.2217/PGS.15.70

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

Linda M. Henricks, Carin A T C Lunenburg, Didier Meulendijks, Hans Gelderblom, Annemieke Cats, Jesse J. Swen, Jan H M Schellens, Henk Jan Guchelaar^*

^*Corresponding author for this work

Pharmacoepidemiology and Clinical Pharmacology

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	1277-1286
Number of pages	10
Journal	Pharmacogenomics
Volume	16
Issue number	11
DOIs	https://doi.org/10.2217/PGS.15.70
Publication status	Published - 1 Jul 2015

Keywords

5-fluorouracil
capecitabine
dihydropyrimidine dehydrogenase
DPYD
fluoropyrimidines
gene activity score
individualized medicine
pharmacogenomics

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10.2217/PGS.15.70

pgs%2E15%2E70Final published version, 1.17 MBLicence: Taverne

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title = "Translating DPYD genotype into DPD phenotype: Using the DPYD gene activity score",

abstract = "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.",

keywords = "5-fluorouracil, capecitabine, dihydropyrimidine dehydrogenase, DPYD, fluoropyrimidines, gene activity score, individualized medicine, pharmacogenomics",

author = "Henricks, {Linda M.} and Lunenburg, {Carin A T C} and Didier Meulendijks and Hans Gelderblom and Annemieke Cats and Swen, {Jesse J.} and Schellens, {Jan H M} and Guchelaar, {Henk Jan}",

year = "2015",

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doi = "10.2217/PGS.15.70",

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T2 - Using the DPYD gene activity score

AU - Henricks, Linda M.

AU - Lunenburg, Carin A T C

AU - Meulendijks, Didier

AU - Gelderblom, Hans

AU - Cats, Annemieke

AU - Swen, Jesse J.

AU - Schellens, Jan H M

AU - Guchelaar, Henk Jan

PY - 2015/7/1

Y1 - 2015/7/1

N2 - 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.

AB - 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.

KW - 5-fluorouracil

KW - capecitabine

KW - dihydropyrimidine dehydrogenase

KW - DPYD

KW - fluoropyrimidines

KW - gene activity score

KW - individualized medicine

KW - pharmacogenomics

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U2 - 10.2217/PGS.15.70

DO - 10.2217/PGS.15.70

M3 - Article

AN - SCOPUS:84941636690

SN - 1462-2416

VL - 16

SP - 1277

EP - 1286

JO - Pharmacogenomics

JF - Pharmacogenomics

IS - 11

ER -

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

Abstract

Keywords

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