天津医药

天津医药 ›› 2021, Vol. 49 ›› Issue (10): 1063-1067.doi: 10.11958/20210640

• 临床研究 • 上一篇    下一篇

JAK2 rs10119004基因多态性对伏立康唑治疗ICU侵袭性真菌感染患者的影响

刘雨，吕冬梅，薛婷，丑晓华，高杏   

  1. 1徐州医科大学（邮编221004）；2徐州医科大学附属医院药学部，3急诊ICU
  • 收稿日期:2021-03-19 修回日期:2021-07-15 出版日期:2021-10-15 发布日期:2021-10-15
  • 通讯作者: 高杏 E-mail:panda864170@126.com
  • 基金资助:
    江苏省药学会奥赛康基金课题

The effect of JAK2 rs10119004 gene polymorphism on voriconazole therapy to ICU patients with invasive fungal infection

LIU Yu, LYU Dong-mei, XUE Ting, CHOU Xiao-hua, GAO Xing   

  1. 1 Xuzhou Medical University, Xuzhou 221004, China; 2 Department of Pharmacy, 3 Emergency Intensive Care Unit, the
    Affiliated Hospital of Xuzhou Medical University
  • Received:2021-03-19 Revised:2021-07-15 Published:2021-10-15 Online:2021-10-15

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摘要： 目的 通过分析JAK2 rs10119004基因多态性对伏立康唑血药谷浓度（Cmin）及临床治疗效果的影响，为伏 立康唑治疗重症监护室（ICU）侵袭性真菌感染个体化方案的制定提供参考。方法 利用PCR及Sanger测序方法检 测JAK2 rs10119004位点的基因型，同时应用液相色谱串联质谱（LC-MS/MS）法检测伏立康唑血药谷浓度（Cmin），分析 各基因型患者 Cmin的特点及不同基因型患者用药后疗效及不良反应发生情况。结果 70 例患者伏立康唑 Cmin为 0.12~12.23 mg/L，平均 3.07（1.92，5.48）mg/L。70 例患者 JAK2 rs10119004 位点基因型共 3 种：野生未突变型 G/G 25 例，杂合子突变型G/A 32例，纯合子突变型A/A 13例。不同Cmin和不同基因型分组患者的治疗有效率及不良反应发 生率差异无统计学意义。不同年龄（Age）、血浆白蛋白（ALB）水平和JAK2 rs10119004基因型患者，其伏立康唑Cmin 存在差异；将具有统计学意义的影响因素纳入多元回归模型，得到回归方程 C1=7.479+0.048×Age-0.233×ALB+ 1.405×X1（X1：G/A=1，非 G/A=0）；C2=7.479+0.048×Age-0.233×ALB+1.208×X2（X2：A/A=1，非 A/A=0）。结论 JAK2 rs10119004基因型可影响ICU侵袭性真菌感染患者伏立康唑的Cmin。

关键词: Janus激酶2, 多态现象, 遗传, 伏立康唑, 血药浓度, 真菌血症

Abstract: Objective To investigate the effects of JAK2 rs10119004 gene polymorphism on voriconzole blood concentration (Cmin) and therapeutic efficiency, and provide a reference for the individualized treatment of intensive care unit (ICU) patients who were diagnosed with invasive fungal infection. Methods The genotypes of JAK2 rs10119004 were detected by PCR and Sanger sequencing methods. The steady-state trough plasma concentration of voriconazole was detected by LC-MS/MS. The characteristics of Cmin, curative effects and adverse reactions in patients with different genotypes were analyzed. Results The trough blood concentration of voriconazole in 70 patients ranged from 0.12 to 12.23 mg/L, with an average of 3.07 (1.92, 5.48) mg/L. JAK2 genotypes were distributed as follows, 25 cases of wild unmutated G/G, 32 cases of heterozygous mutant G/A and 13 cases of homozygous mutant A/A. There were no significant differences in the effective rate of treatment and the incidence of adverse reactions between patients with different blood drug concentrations and different genotypes. There were significant differences in the plasma concentration of voriconazole between patients with different ages, plasma albumin (ALB) levels and JAK2 rs10119004 genotypes. The statistically significant influencing factors were included in the multiple regression model to obtain the final regression model C1=7.479+0.048×Age-0.233×ALB+ 1.405×X1 and C2=7.479+0.048×Age-0.233×ALB+1.208×X2 (X1: G/A=1, non G/A=0; X2: A/A=1, non A/A=0). Conclusion The genotypes of JAK2 rs10119004 can affect the Cmin of voriconazole in patients with invasive fungal infection in ICU.

Key words: Janus kinase 2, polymorphism, genetic, voriconazole, plasma concentration, fungemia