CAJ | 학술논문

目的探讨白细胞介素-6(IL-6) rsl800796位点单核苷酸多态性(SNPs)对肝移植术后他克莫司(FK506)浓度/剂量(C/D)比值的影响.方法采用酶联免疫吸附试验试剂盒,检测79例肝移植患者术后FKS06的全血浓度,并记录术后4周内全血谷浓度和给药剂量.检测供受体rsl800796位点的SNPs,并比较该位点SNPs对FKS06 C/D值的影响.采用荧光定量聚合酶链反应(FQ-PCR)和免疫组织化学染色检测供肝组织IL-6 mRNA和蛋白表达.结果肝移植术后第2和3周,仅供体IL-6 rs1800796位点SNPs与FK506相关(P＜0.05),而与受体无相关.快代谢组供肝组织IL-6表达(△Ct值6.6±1.2)高于慢代谢组(△Ct值7.7±1.1),差异有统计学意义(P＜0.05).免疫组织化学显示IL-6在快代谢组肝组织的中等表达率为80.0％(24/30),高于慢代谢组[48.4％(15/31)],差异有统计学意义(P＜0.05).结论供体IL-6 rs1800796位点SNPs与肝移植术后早期他克莫司C/D值密切相关.
목적 탐토백세포개소-6(IL-6) rsl800796위점단핵감산다태성(SNPs)대간이식술후타극막사(FK506)농도/제량(C/D)비치적영향.방법 채용매련면역흡부시험시제합,검측79례간이식환자술후FKS06적전혈농도,병기록술후4주내전혈곡농도화급약제량.검측공수체rsl800796위점적SNPs,병비교해위점SNPs대FKS06 C/D치적영향.채용형광정량취합매련반응(FQ-PCR)화면역조직화학염색검측공간조직IL-6 mRNA화단백표체.결과 간이식술후제2화3주,부공체IL-6 rs1800796위점SNPs여FK506상관(P＜0.05),이여수체무상관.쾌대사조공간조직IL-6표체(△Ct치6.6±1.2)고우만대사조(△Ct치7.7±1.1),차이유통계학의의(P＜0.05).면역조직화학현시IL-6재쾌대사조간조직적중등표체솔위80.0％(24/30),고우만대사조[48.4％(15/31)],차이유통계학의의(P＜0.05).결론 공체IL-6 rs1800796위점SNPs여간이식술후조기타극막사C/D치밀절상관.
Objective To investigate the effect of interleukin (IL)-6 rsl800796 locus single nucleotide polymorphisms (SNPs) in the donors and recipients on concentration/dose (C/D) ratios of tacrolimus after liver transplantation.Methods A total of 79 liver transplantation patients whose whole blood concentrations of tacrolimus were determined by using enzyme-linked immunosorbent assay kits were enrolled in the study.Additionally,tacrolimus dosage and trough blood concentration of them was recorded and studied at four weeks after liver transplantation.The SNPs at IL-6 rs1800796 locus were genotyped in both donors and recipients.Then we compared the influence of the different genotypes at this locus on FK506 C/D value for patients.Fluorescent quantitative polymerase chain reaction (FQ-PCR) and immunohistochemical methods were used to test the IL-6 expression levels of mRNA and protein.Results Only donor IL-6 rs1800796 SNPs was associated with tacrolimus C/D ratios at week 2 and 3 after liver transplantation (P ＜ 0.05).While this phenomenon was not finded in recipients from week 1 to 4.The △Ct value in the fast metabolism group contained carriers of genotype CC is (6.6 ± 1.2),while in the slow metabolism group clustered carriers of genotype CG/GG is (7.7 ± 1.1).The difference was significant (P ＜ 0.05).The intermediate expression rate of IL-6 protein in fast metabolism group [80.0％ (24/30)] was higher than that in slow metabolism group [48.4％ (15/31)].There was significant difference (P ＜ 0.05).Conclusion Donor IL-6 rs1800796 SNPs were closely associated with tacrolimus C/D ratios in the early stage after liver transplantation.