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.