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