急性移植物抗宿主病细胞因子基因多态性与环孢素A血药浓度的相关性研究

Correlation between cytokine gene polymorphism of aGVHD and blood concentration of cyclosporine A

目的：探讨异基因造血干细胞移植（allo-HSCT）中急性移植物抗宿主病细胞因子基因多态性与环孢素A的关系。方法：选取2014年1月至2015年12月行allo-HSCT受者32例作为研究对象,采用聚合酶链式反应（PCR）联合基因测序法检测目的基因特殊SNP位点基因分型,测定术后早期出现aGVHD的重要时期CsA的血药浓度,观察受者术后出现aGVHD的情况,比较TGF-β1＋869（C/T）不同基因分型CsA血药浓度的差异,分析TGF-β1＋869（C/T）基因多态性与CsA的关系及对aGVHD的影响。结果：本组32例患者的TGF-β＋869基因多态性研究结果为16例C/C基因型占50.00%,9例T/T基因型占28.12%,7例C/T基因型占21.88%;C/T型患者中的4例出现重度aGVHD占57.14%,发生率与C/C型、T/T型患者比较有显著性差异（P〈0.01）。3种基因型患者的CsA血药谷浓度均能达到200~300μg·L-1的目标值,比较3种基因型患者的CsA血谷浓度,C/T型及T/T型患者均高于C/C型患者（P〈0.01）。结论：本组患者发生重度aGVHD与CsA血药浓度无明显相关性,TGF-β1＋869基因型为C/T杂合子的allo-HSCT受者预防GVHD应调整免疫抑制方案,加用霉酚酸酯或使用其它免疫抑制剂以减少重度aGVHD发生。

OBJECtIVE To investigate the relationship between the cytokine gene polymorphism of the acute graft versus host disease（aGVHD） and cyclosporine A（CsA） in allogeneic hematopoietic stem cell transplantation（allo-HSCT）. METItODS 32 cases of recipients received allo-HSCT in January 2014 to December 2015 were selected as objects of study. We detected genotypes on specific SNP of target gene by polymerase chain reaction（PCR） combined with gene sequencing, measured blood concentration of CsA on the critical period that aGVHD occurred early after operation and observed the occurrence of aGVHD in postoperative recipients. The differences on blood concentration of CsA in multiple genetypes of TGF-β1 ＋ 869（C/T） were compared and t.he correlation between gene polymorphism of TGF-β1 ＋ 869（C/T） with CsA and its effect on aGVHD was ana- lyzed. RESULTS The research on 32 cases of TGF-β1 ＋ 869 gene polymorphism show that 16 cases of C/C genotype accounted for 50%,9 cases of T/T genotype accounted for 28. 12% and 7 cases of C/T genotype accounted for 21.88%. Four patients with C/T occurred severe aGVHD accounted for 57. 14%, which was significantly different from patients with C/C and T/T（P 〈0. 01）. CsA blood trough concentration of three genotypes in patients can reach the target value of 200 to 300 μg·L-1, which were higher in patients with T/T and C/T genotype than C/C genotype（P〈0. 01）. CONCLUSION No correlation was found between occurrence of severe aGVHD and blood concentration of CsA in our group. Immunosuppressive regimen for prevention of aGVHD should be adjusted in allo-HSCT recipients which .manifested as C/T genotype in TGF-β1 ＋ 869 and mycophenolate mofetil（MMF） or other immunosuppressive agents should be added to reduce severe aGVHD.