Association of CYP2C19 and UGT1A4 Polymorphisms with Voriconazole-Induced Liver Injury

Abstract

Aim: This study investigated the association between voriconazole-induced liver injury and gene polymorphisms of CYP2C19 and UGT1A4. Materials & methods: Thirty-eight adult patients who received voriconazole therapy were included in the study. Genotype of CYP2C19 was detected using gene chip hybrid analysis. The UGT1A4 142T>G was genotyped using PCR-RFLP analysis. Results: Ten patients (26.3%) had voriconazole-induced liver injury and were considered as the case group There was no significant difference between the two groups in genotype and allele frequencies of CYP2C19*2 and UGT1A4 142T>G (p > 0.05), however, the GA frequency of CYP2C19 *3 in the drug-induced liver injury case group was higher than that in the control group (p < 0.05). Compared with patients carrying *1/*1 or *1/*2, there was no significant difference in voriconazole trough concentration of the patients with *1/*3 (p > 0.05). Conclusion: There was no significant correlation between voriconazole-induced liver injury and gene polymorphisms of CYP2C19 and UGT1A4.

A validation study of the UGT1A4 rs2011404 variant and the risk of anti‐tuberculosis drug‐induced hepatotoxicity in an Eastern Chinese Han population

“…Song et al investigated the association between voriconazole‐induced liver injury and gene polymorphisms of UGT1A4. However, no significant correlation was found between voriconazole‐induced liver injury and polymorphisms of UGT1A4 13 . Additionally, in a previous study to be validated, the role of SNP rs2011404 in the UGT1A4 gene was different between 41 ATDH cases and 39 healthy controls 10 .…”

“…However, no significant correlation was found between voriconazole-induced liver injury and polymorphisms of UGT1A4. 13 Additionally, in a previous study to be validated, the role of SNP rs2011404 in the UGT1A4 gene was different between 41 ATDH cases and 39 healthy controls. 10 Considering the small sample size and different control selections, the actual impact of such findings on ATDH must be validated.…”

“…12 To date, in addition to the study concerning the role of SNP rs2011404 in ATDH, 10 another study investigated the genetic susceptibility to liver injury. 13 Song et al investigated the association between voriconazole-induced liver injury and gene polymorphisms of UGT1A4. However, no significant correlation was found between voriconazole-induced liver injury and polymorphisms of UGT1A4.…”

“…For example, a previous study indicated that the decreased kinetic parameters (Cl int ) of UGT1A4*2 and UGT1A4*3 in lamotrigine glucuronidation might lead to interindividual variations in lamotrigine metabolism in vivo 12 10 another study investigated the genetic susceptibility to liver injury 13 . Song et al investigated the association between voriconazole‐induced liver injury and gene polymorphisms of UGT1A4.…”

Impact of cytochrome P450 2C19 polymorphisms on the clinical efficacy and safety of voriconazole: an update systematic review and meta-analysis

“…Our meta-analysis exhibited no statistically significant differences at all comparisons. However, the PMs showed a toward of higher risk of hepatotoxicity than NMs in all studies (RR: 1.60, 95%CI: 0.94˜2.74,I 2 =27%, p=0.08) [20][21][22][23][34][35][36] . Sensitivity analysis showed the results did not alter significantly in all comparisons, but, the result of the comparison between PMs and NMs (RR: 2.38, 95%CI: 1.25˜4.52,I 2 =0%, p=0.008) became statistically significant after excluding study by Kim et al 35 .…”