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[摘要]
目的：探讨蛋白酪氨酸激酶2/信号转导子与激活子3(Janus kinase signal transducers 2 and activator of transcription 3， JAK2/STAT3)基因多态性对真菌性角膜溃疡患者伏立康唑血药浓度的影响。
方法：选取2012-03/2015-02间我院诊治的56例56眼真菌性角膜溃疡患者为研究对象，采用高效液相色谱-荧光检测法测定每位患者伏立康唑的血药浓度，同时利用聚合酶链式反应-限制性片段长度多态性方法(PCR-RFLP)分别进行JAK2/STAT3基因型分析。
结果：将所有患者以中位标准化伏立康唑血药浓度为分界值，分为高血药浓度组(35例，62%)和低血药浓度组(21例，38%)； 高、低血药浓度组患者在男性比例、身高、体质量、千克体质量日剂量和不良反应发生情况方面的比较无显著统计学差别(P>0.05)； 高血药浓度组的中位谷浓度和中位标准化血药浓度都显著高于低血药浓度组(P<0.05)； 高血药浓度组患者伏立康唑的有效率也优于低血药浓度组(P<0.05)； 在JAK2-STAT3基因7个多态位点分型中，高血药浓度组患者JAK2 rs10119004位点GG和GA等位基因、STAT3 rs12948909位点TT等位基因与低血药浓度组比较，差异均有统计学意义(P<0.05)。
结论：JAK2-STAT3基因多态性对伏立康唑血药浓度和临床疗效均有明显影响，提示药物遗传学研究对伏立康唑的临床合理用药有重要指导意义。
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[Abstract]
AIM: To investigate the effects of Janus Kinase 2-Signal Transducers and Activator of Transcription 3(JAK2/STAT3)gene polymorphism on the voriconazole plasma concentration in patient with fungal corneal ulcer.
METHODS: A total of 56 cases(56 eyes)with fungal corneal ulcer wererecruited in our hospital from March 2012 to February 2015. The concentration of voriconazole plasma in each patient was detected by high performance liquid chromatography with fluorescence detection. Meanwhile, the JAK2/STAT3 genotype analysis was performed by polymerase chain reaction restriction fragment length polymorphism(PCR-RFLP).
RESULTS:All patients were divided into high voriconazole plasma concentration group(35 cases, 62.50%)and low voriconazole plasma concentration group(21 cases, 37.50%)by using standard median as boundary value. There was no significant difference on the male proportion, height, weight, daily dose and adverse reaction of the patients between high and low serum voriconazole concentration group(P>0.05). The median trough concentration and the median standardized serum concentration in the high serum voriconazole concentration group were significantly higher than those of the low serum voriconazole concentration group(P<0.05). The effective rate of high serum voriconazole concentration group was better than that of low serum voriconazole concentration group(P<0.05). In the seven polymorphic loci of JAK2-STAT3 gene, the JAK2, rs10119004, GA allele, GG allele and the STAT3, rs12948909 TT allele of high serum voriconazole concentration group showed significant difference as compared with the low serum voriconazole concentration group(P<0.05).
CONCLUSION:The JAK2-STAT3 gene polymorphism shows significant effects on the serum voriconazole concentration and clinical efficacy of voriconazole, indicating that pharmacogenetic study of great significance for clinical rational used of voriconazole.
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