肾移植术后非结合性高胆红素血症UGT1A1基因多态性的临床研究

Clinical study of UGT1A1 gene polymorphism in unconjugated hyperbilirubinemia after renal transplantation

目的分析肾移植术后合并非结合性高胆红素血症受者UGT1A1*6和UGT1A1*28基因突变情况,并探讨其临床意义。方法采用数字荧光分子杂交测序技术对北京大学中日友好医院21例肾移植术后合并非结合性高胆红素血症的受者血液样本进行UGT1A1*6和UGT1A1*28目的基因片段序列的检测,以确定受者的UGT1A1*6和UGT1A1*28基因的突变情况。结果检测结果发现3例UGT1A1*28和UGT1A1*6的联合杂合突变型,4例UGT1A1*28基因杂合突变型,2例UGT1A1*6杂合突变型,以及4例UGT1A1*6的纯合突变型。其中,UGT1A1*28基因突变率为33%(7/21),UGT1A1*6基因突变率为43%(9/21),两者总的突变率达62%(13/21)。结论 UGT1A1多态性与受者肾移植术后合并非结合性高胆红素血症有关。检测肾移植受者血液样本中的UGT1A1*6和UGT1A1*28基因片段的序列,有助于明确肾移植术后受者出现非结合性高胆红素血症的病因,帮助Gilbert综合征的诊断、排除免疫抑制药物对肝功能的影响,从而指导肾移植受者临床用药方案。

Objective To explore the gene mutations of UGT1A1*6 and UGT1A1*28 in patients with unconjugated hyperbilirubinemia after renal transplantation and understand their clinical significance.Methods UGT1A1*6 and UGT1A1*28 gene fragments in blood samples of patients with unconjugated hyperbilirubinemia after renal transplantation were detected by digital fluorescent molecular hybridization sequencing.Results A total of 21 patients with unconjugated hyperbilirubinemia after renal transplantation were examined for UGT1A1*6 and UGT1A1*28 alleles.The results showed that there were 3 UGT1A1*28 and UGT1A1*6 combined heterozygous mutations,4 UGT1A1*28 gene heterozygous mutations,2 UGT1A1*6 heterozygous mutations and 4 UGT1A1*6 homozygous mutations.Among them,the mutation rates of UGT1A1*28 gene and UGT1A1*6 gene were 33%(7/21)and 43%(9/21)respectively and the total mutation rate of both was 62%(13/21).Conclusions UGT1A1 polymorphism is associated with unconjugated hyperbilirubinemiaafter renal transplantation.By detecting the sequence of UGT1A1*6 and UGT1A1*28 gene fragments in blood samples of renal transplant patients,it is helpful to clarify the etiology of unconjugated hyperbilirubinemia after renal transplantation to confirm the diagnosis of Gilbert syndrome and rule out the effect of immunosuppressive drugs on liver function so as to guide the clinical medication of renal transplant patients.