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

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

目的通过分析JAK2 rs10119004基因多态性对伏立康唑血药谷浓度(C_(min))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(C_(min)),分析各基因型患者C_(min)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C_(min)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C_(min)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C_(min)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JAK2rs10119004基因型可影响ICU侵袭性真菌感染患者伏立康唑的C_(min)。

Objective To investigate the effects of JAK2 rs 10119004 gene polymorphism on voriconzole blood concentration(C_(min))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 C_(min),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 xAge-0.233 xALB+1.405×X1 and C2=7.479+0.048 xAge-0.233 xALB+1.208 xX2(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 C_(min)of voriconazole in patients with invasive fungal infection in ICU.