2026-10-14T06:08:07Z
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2026-10-01T13:19:53Z
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Analysis of the influence of rs1801265 polymorphism on DPD enzyme activity and contributing factors in the Chinese population
Linkun Pan (25156644)
Yang Shen (66591)
Haibo Jiang (574973)
Fangling Wu (8199012)
Nan Wang (21935)
Mengzhen Zhang (12041408)
Kui Yang (83118)
Jiajie Luan (6709523)
Maodi Xu (14012820)
Medicine
Cell Biology
Genetics
Pharmacology
Cancer
DPYD
DPD activity
5-fluorouracil
SNP loci
Chinese population
personalized medicine
<p>Dihydropyrimidine dehydrogenase (DPD), encoded by DPYD, is essential for 5-fluorouracil (5-FU) metabolism, yet functional variants remain understudied in Chinese populations.</p> <p>We enrolled 300 healthy Chinese subjects and measured DPD activity as the HPLC-based 5-FU degradation rate in PBMCs. Five DPYD SNPs selected from NCBI and PharmGKB were genotyped by SNaPshot; genotype–degradation-rate associations were assessed by univariate and multivariable regression with FDR correction, and functional consequences predicted using PolyPhen-2, SIFT, SWISS-MODEL and molecular docking.</p> <p>The median degradation rate was 1.140 ng/mL/10<sup>6</sup> cells/min. c.85T > C (rs1801265) was the only variant associated with a higher degradation rate (<i>p</i> = 0.0041) and remained independently associated in the multivariable model; it is common in Asians (MAF ~7%). In 39 colorectal cancer patients receiving 5-FU-based chemotherapy, carriers showed numerically lower 5-FU AUC and shorter progression-free survival, without statistical significance. Molecular modeling predicted that the Cys29Arg substitution alters DPD conformation and 5-FU binding.</p> <p><i>DPYD</i> c.85T > C (rs1801265) was associated with higher 5-FU degradation capacity in Chinese subjects and is predicted to increase DPD activity. If confirmed, this gain-of-function effect may reduce fluoropyrimidine toxicity but could also warrant dose escalation to maintain efficacy; direct functional assays and prospective patient-cohort validation are required before clinical use.</p>
2026-10-01T13:19:53Z
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10.6084/m9.figshare.34045983.v1
https://figshare.com/articles/figure/Analysis_of_the_influence_of_rs1801265_polymorphism_on_DPD_enzyme_activity_and_contributing_factors_in_the_Chinese_population/34045983
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