Objective To explore the effect and potential mechanism of CYP2C19 gene polymorphism on the blood minimum concentration of voriconazole in children with invasive pulmonary fungal infection. Methods The clinical data of 58 children, who used voriconazole for treatment and prevention of invasive fungal infection in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University from September 2013 to September 2021, were collected and analyzed retrospectively, including demographic information, glutamic-pyruvic transaminase (ALT), C-reactive protein (CRP) and interleukin-6 (IL-6). The CYP2C19 genotype of children was detected by gene chip method, and the blood drug concentration was detected by high performance liquid chromatography. According to the drug concentration, the children were divided into low concentration group and normal concentration group. The difference of blood drug concentration in patients with different genotypes was compared. Binary logistic regression analysis was performed to analyze the factors affecting the blood concentration of voriconazole in children. Results Four of the 58 children refused to make gene test, the rest 54 patients including 35 males and 19 females; Among the six CYP2C19 genotypes, most children were with *1/*1 (636 GG, 681 GG) genotype (30 cases); The others were *1/*2 (636 GG, 681 GA) genotype (20 cases), *1/*3 (636 GA, 681 GG) genotype (2 cases), and *2/*3 (636 GA, 681 GA) genotype (2 cases), children without *2/*2 (636 GG, 681 AA) genotype and *3/*3 (636 AA, 681 GG) genotype. Among the gene phenotypes, extensive metabolizer type was the highest (30 cases), followed by intermediate metabolizer type and poor metabolizer type (22 cases and 2 cases, respectively). The frequency of allele CYP2C19*1 was the highest (82 cases), followed by the allele CYP2C19*2 and CYP2C19*3 (22 cases and 4 cases, respectively). Genotype and allele were significantly correlated with voriconazole minimum concentration. Compared with intermediate metabolizer and poor metabolizer, extensive metabolizer significantly reduced voriconazole minimum concentration. Compared with CYP2C19*2 and CYP2C19*3 alleles, CYP2C19*1 allele significantly reduced the concentration of voriconazole. Binary logistic regression analysis demonstrated that BMI, CRP, IL-6 and genotype can significantly affect the blood minimum concentration of voriconazole. Conclusions The genotype of CYP2C19 is mainly *1/*1 (636 GG, 681 GG), the extensive metabolizer genotype is the most, and the allele of CYP2C19*1 is the most common. Inflammatory factors, BMI and genotype significantly affected voriconazole metabolism.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |