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Effect of CYP2C19 gene polymorphism on the blood minimum concentration of voriconazole in children with invasive pulmonary fungal infection and its potential mechanisms
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Sen Yang1, Shang-Zhi Wu1, Zhan-Hang Huang1, Yu-Neng Lin1, Xiao-Wen Chen1, Jin-Li Tan2, Qing-Yun Xu1, Cheng-Yu Lu1, De-Hui Chen1, *
Medical Journal of Chinese People’s Liberation Army | 2023, 48(10) : 1174 - 1179
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Medical Journal of Chinese People’s Liberation Army | 2023, 48(10): 1174-1179
Clinical Research
Effect of CYP2C19 gene polymorphism on the blood minimum concentration of voriconazole in children with invasive pulmonary fungal infection and its potential mechanisms
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Sen Yang1, Shang-Zhi Wu1, Zhan-Hang Huang1, Yu-Neng Lin1, Xiao-Wen Chen1, Jin-Li Tan2, Qing-Yun Xu1, Cheng-Yu Lu1, De-Hui Chen1, *
Affiliations
  • 1Department of Pediatrics, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China
  • 2Clinical Laboratory, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China
Published: 2023-10-28 doi: 10.11855/j.issn.0577-7402.1861.2023.0427
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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.

gene, CYP2C19  /  polymorphism  /  voriconazole  /  blood minimum concentration
Sen Yang, Shang-Zhi Wu, Zhan-Hang Huang, Yu-Neng Lin, Xiao-Wen Chen, Jin-Li Tan, Qing-Yun Xu, Cheng-Yu Lu, De-Hui Chen. Effect of CYP2C19 gene polymorphism on the blood minimum concentration of voriconazole in children with invasive pulmonary fungal infection and its potential mechanisms[J]. Medical Journal of Chinese People’s Liberation Army, 2023 , 48 (10) : 1174 -1179 . DOI: 10.11855/j.issn.0577-7402.1861.2023.0427
  • National Natural Science Foundation of China(81770063)
  • Basic and Applied Research Foundation of Guangdong Province Zhong Nan-Shan Medical Foundation(202102010343)
Year 2023 volume 48 Issue 10
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Article Info
doi: 10.11855/j.issn.0577-7402.1861.2023.0427
  • Receive Date:2022-09-06
  • Online Date:2025-11-25
  • Published:2023-10-28
Article Data
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History
  • Received:2022-09-06
  • Accepted:2022-12-06
Funding
National Natural Science Foundation of China(81770063)
Basic and Applied Research Foundation of Guangdong Province Zhong Nan-Shan Medical Foundation(202102010343)
Affiliations
    1Department of Pediatrics, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China
    2Clinical Laboratory, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China

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表12种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
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Genus
种数
Number of
species
占总种数比例
Percentage of total
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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
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