JAK2-STAT3基因多態性對真菌性角膜潰瘍患者伏立康唑血藥濃度的影響

彭 璟，李爽樂，曾洪波，鄧應平

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·臨床論著·

JAK2-STAT3基因多態性對真菌性角膜潰瘍患者伏立康唑血藥濃度的影響

彭 璟1,2，李爽樂2，曾洪波2，鄧應平1

?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.

目的：探討蛋白酪氨酸激酶2/信號轉導子與激活子3(Janus kinase signal transducers 2 and activator of transcription 3, JAK2/STAT3)基因多態性對真菌性角膜潰瘍患者伏立康唑血藥濃度的影響。

方法：選取2012-03/2015-02間我院診治的56例56眼真菌性角膜潰瘍患者為研究對象，采用高效液相色譜-熒光檢測法測定每位患者伏立康唑的血藥濃度，同時利用聚合酶鏈式反應-限制性片段長度多態性方法(PCR-RFLP)分別進行JAK2/STAT3基因型分析。

結果：將所有患者以中位標準化伏立康唑血藥濃度為分界值，分為高血藥濃度組(35例，62%)和低血藥濃度組(21例，38%)；高、低血藥濃度組患者在男性比例、身高、體質量、千克體質量日劑量和不良反應發生情況方面的比較無顯著統計學差別(P>0.05)；高血藥濃度組的中位谷濃度和中位標準化血藥濃度都顯著高于低血藥濃度組(P<0.05)；高血藥濃度組患者伏立康唑的有效率也優于低血藥濃度組(P<0.05)；在JAK2-STAT3基因7個多態位點分型中，高血藥濃度組患者JAK2 rs10119004位點GG和GA等位基因、STAT3 rs12948909位點TT等位基因與低血藥濃度組比較，差異均有統計學意義(P<0.05)。

結論：JAK2-STAT3基因多態性對伏立康唑血藥濃度和臨床療效均有明顯影響，提示藥物遺傳學研究對伏立康唑的臨床合理用藥有重要指導意義。

真菌性角膜潰瘍；伏立康唑；JAK2；STAT3

引用：彭璟，李爽樂，曾洪波，等.JAK2-STAT3基因多態性對真菌性角膜潰瘍患者伏立康唑血藥濃度的影響.國際眼科雜志2016;16(12):2204-2208

0引言

真菌性角膜潰瘍是一種主要由真菌引發的感染性角膜病變，具有發病率高、病程長、缺乏敏感性抗真菌藥物等特點，也是導致我國角膜盲的首位病因。目前，臨床上治療真菌性角膜潰瘍的方式有兩種，主要包括手術治療(角膜移植術或清創術)和抗真菌藥物治療[1]。其中……