Genetic polymorphisms of transient receptor potential melastatin 1 correlate with voriconazole‐related visual adverse events

• Published in: Mycoses 2020-06, Vol.63 (6), p.579-587
• Main Authors: Jiang, Ying‐Kui, Wang, Rui‐Ying, Wang, Xuan, Zhao, Hua‐Zhen, Zhou, Ling‐Hong, Huang, Li‐Ping, Yip, Ching‐Wan, Cheng, Jia‐Hui, Que, Chun‐Xing, Jiang, Chen, Zhu, Li‐Ping
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents - adverse effects; Female; Genotype; Genotype & phenotype; Genotyping; Hallucinations; Hallucinations - chemically induced; Hallucinations - genetics; Humans; Invasive Fungal Infections - drug therapy; Male; Middle Aged; Polymorphism, Single Nucleotide; Prospective Studies; serum concentration; Single-nucleotide polymorphism; Transient receptor potential proteins; TRPM Cation Channels - genetics; TRPM1; visual adverse events; Voriconazole; Voriconazole - adverse effects; Voriconazole - blood; Young Adult
• ISSN: 0933-7407; 1439-0507
• DOI: 10.1111/myc.13080

Summary Background Causes of voriconazole‐related visual adverse events (VVAE) remained controversial. Objectives We aimed to explore the relationship between voriconazole serum concentrations and VVAE as well as the potential influence of transient receptor potential melastatin 1 (TRPM1) on VVAE. Patients/methods This prospective observational cohort study was done in two stages. Patients who received voriconazole for invasive fungal diseases were consecutively enrolled. Correlations between voriconazole trough levels and VVAE were explored in 76 patients. Genotyping was further conducted for 17 tag SNPs of TRPM1 in a larger population of 137 patients. Genotype distributions were compared between patients with and without VVAE. Result Of the 76 patients, a total of 229 steady‐state voriconazole trough levels were evaluated, 69.9% of which were within the target range (1‐5.5 mg/L). No correlations were found between voriconazole trough levels and VVAE. Of the total 137 patients, VVAE occurred in 37 (27.0%) patients, including visual hallucination (13.9%, 19/137) and visual disturbances (19.0%, 26/137). Significant difference in TRPM1 genotype distribution was only observed in patients with visual hallucination but not with visual disturbances. We found that rs890160 G/T genotype was under‐presented (OR, 0.11; 95% CI, 0.01‐0.84; P = .011) and rs1378847 C/C genotype was more frequently detected (OR, 8.89; 95% CI, 1.14‐69.02; P = .013) in patients with visual hallucination when compared with those without. Conclusion Transient receptor potential melastatin 1 was genetically associated with voriconazole‐related visual hallucination. The correlation was failed to found between voriconazole trough levels and VVAE.