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目的探索妊娠滋养细胞疾病患者的二氢嘧啶脱氢酶基因(DPYD)多态性。方法采用多聚酶链反应(PCR)一直接测序方法检测DPYD中A74G,T85C(DPYD~*9),IVS14+1G→A(DPYD~*2),C2303A和A2846T等5个位点的突变频率,并对DPD活性缺乏以及使用氟化嘧啶类药物出现严重不良反应的回访患者的DPYD基因中外显子4、外显子5、外显子6、外显子7、外显子8、外显子10、外显子11、外显子12、外显子13、外显子21和外显子23进行分析。结果130名妊娠滋养细胞疾病患者中,化疗组患者105名,使用含氟化嘧啶类药物治疗发生严重不良反应的回访患者25名。患者中存在DPYD~*2,DPYD~*9,A496G,A1627G和C2303A等位点变异,新发现A720C和A2670C 2种同义突变。化疗组患者DPYD~*9等位基因发生频率为6.93%,C2303A发生频率为0.49%;未发现DPYD~*2、A74G和A2846T位点变异。DPYD~*2, DPYD~*9,A496G,A720C,A1627G,C2303A和A2670C在DPD活性缺乏及曾出现严重不良反应的回访患者中的发生频率分别为1.14%,7.95%,3.41%,37.50%,18.1 8%,1.14%和15.91%。结论在中国妊娠滋养细胞疾病患者中发现DPYD~*2, DPYD~*9,A496G,A1627G等位点变异,首次在中国人群中发现C2303A,A720C和A2670C变异。DPYD~*2和C2303A变异可能与DPD活性缺乏相关。
Objective To explore the dihydropyrimidine dehydrogenase gene (DPYD) polymorphism in patients with gestational trophoblastic disease. Methods The mutation frequency of 5 sites including A74G, T85C (DPYD ~ * 9), IVS14 + 1G → A (DPYD ~ * 2), C2303A and A2846T in DPYD was detected by polymerase chain reaction (PCR) Exon 4, Exon 5, Exon 6, Exon 7, Exon 8, Exon 10 in the DPYD gene in patients with DPD that lacked DPD activity and had serious adverse reactions to fluoropyrimidine drugs , Exon 11, exon 12, exon 13, exon 21 and exon 23 were analyzed. Results Of the 130 patients with gestational trophoblastic disease, there were 105 patients in the chemotherapy group and 25 patients were retrospectively treated with fluoropyrimidine-containing drugs for serious adverse reactions. In patients with DPYD ~ * 2, DPYD ~ * 9, A496G, A1627G and C2303A and other site mutations, newly discovered A720C and A2670C two kinds of synonymous mutations. In the chemotherapy group, the frequency of DPYD * 9 alleles was 6.93% and the frequency of C2303A was 0.49%. No mutation in DPYD ~ * 2, A74G and A2846T sites was found. The frequency of DPYD ~ * 2, DPYD ~ * 9, A496G, A720C, A1627G, C2303A and A2670C were 1.14%, 7.95%, 3.41% and 37.50% in the patients with DPD activity deficit and those who had serious adverse reactions. 18.1 8%, 1.14% and 15.91%. Conclusions Mutations of DPYD * 2, DPYD * 9, A496G and A1627G were found in gestational trophoblastic disease in China, and the variations of C2303A, A720C and A2670C were found in Chinese population for the first time. DPYD ~ * 2 and C2303A mutations may be related to the lack of DPD activity.