将二氢嘧啶脱氢酶（DPYD）基因型转化为二氢嘧啶脱氢酶（DPD）表型：使用二氢嘧啶脱氢酶（DPYD）基因活性评分。
Translating DPYD genotype into DPD phenotype: using the DPYD gene activity score.
作者信息
Henricks Linda M, Lunenburg Carin A T C, Meulendijks Didier, Gelderblom Hans, Cats Annemieke, Swen Jesse J, Schellens Jan H M, Guchelaar Henk-Jan
机构信息
Division of Clinical Pharmacology, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Department of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
出版信息
Pharmacogenomics. 2015;16(11):1277-86. doi: 10.2217/pgs.15.70. Epub 2015 Aug 12.
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 DPYD2A, DPYD13, 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.
二氢嘧啶脱氢酶（DPD，由基因DPYD编码）在氟嘧啶的代谢中起关键作用。4%至5%的人群存在DPD缺乏症，且与严重的氟嘧啶相关毒性有关。已描述了DPYD中的几个单核苷酸多态性（SNP），这些SNP会导致酶活性缺失或降低，包括DPYD2A、DPYD13、c.2846A>T和c.1236G>A/单倍型B3。由于这些SNP对DPD酶活性的影响不同，建议进行差异化剂量调整。我们提出了基因活性评分法，用于将DPYD基因型转化为表型，同时考虑SNP功能上的差异。该方法可用于规范个体化氟嘧啶剂量调整，从而实现最佳的安全性和有效性。
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