Analysis of the influence of rs1801265 polymorphism on DPD enzyme activity and contributing factors in the Chinese population

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/10⁶ 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.