Specific CYP450 Genotypes in the Chinese Population Affect Sorafenib Toxicity in HBV/HCV-associated Hepatocellular Carcinoma Patients

Biomedical and Environmental Sciences : BES
Xing Gang GuoHui Liu

Abstract

The purpose of this study was to screen for frequencies of different CYP450 genotypes in the Chinese population and explore the relationship between sorafenib toxicity and CYP450 polymorphism. A total of 600 peripheral blood samples were obtained from two groups for this study. The first group of 300 samples were from Chinese patients with HBV/HCV-associated HCC, while the remaining 300 samples were from a healthy population of recruited subjects. Allele-specific PCR and long-fragment gene sequencing was used to identify the frequencies of CYP450 polymorphism. Aflatoxin-induced HCC rat models expressing CYP3A4*1, CYP3A5*3, CYP2C19*2, and CYP2D6*10 were established and treated with sorafenib at certain time points. Hepatic and renal function, along with plasma concentration of sorafenib, were monitored regularly. The most common forms of CYP mutations in the Chinese population were identified. The levels of sorafenib plasma concentration, as well as damage to hepatic and renal function in aflatoxin-induced HCC rat models varied significantly across the different CYP genotypes. The mutational frequencies of CYP3A5, CYP3A4, CYP2C19, and CYP2D6 genotypes varied among different ethnic groups and populations. Individuals with CYP3A5*...Continue Reading

Citations

Aug 16, 2019·World Journal of Gastroenterology : WJG·Elena De MattiaGiuseppe Toffoli
Jun 19, 2020·Cancers·Loraine Kay D CabralCaecilia H C Sukowati
Jun 27, 2020·Cancers·Jose J G MarinOscar Briz

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