侵袭性真菌感染患者细胞色素P_(450)2C19遗传多态性分析

目的 探讨细胞色素P_(450)2C19(CYP2C19)遗传多态性在侵袭性真菌感染患者中的分布情况.方法 采用PCR-限制性片段长度多态性(PCR-RFLP)技术检测134例侵袭性真菌感染患者和134例健康对照者CYP2C19基因2个主要单核苷酸多态性位点CYP2C19*2和CYP2C19*3的基因型,比较两组各等位基因频率及代谢型的比例.结果 侵袭性真菌感染病例组CYP2C19*1等位基因频率为58.2%,CYP2C19*2等位基因频率为36.6%,CYP2C19*3 等位基因频率为5.2%.对照组CYP2C19*1等位基因频率为63.4%,CYP2C19*2 等位基因频率为34.3%,CYP2C19*3 等位基因频率为2.2%,两组间差异无统计学意义.侵袭性真菌感染组纯合快代谢、杂合快代谢以及慢代谢型比例分别为33.6%、50.0%、16.4%,对照组比例为40.3%、48.5%、11.2%,两组差异无统计学意义.结论 在本组侵袭性真菌感染患者以及健康人群中存在明显CYP2C19遗传多态性,且近2/3患者为杂合快代谢型或慢代谢型.因此,在治疗过程中应重视CYP2C19遗传多态性对药物代谢的影响.

The polymorphism of cytochrome P_(450)2C19 gene in pafients with invasive fungal infections

Objective To investigate the polymorphism profile of cytochrome P_(450)2C19 (CYP2C19) in Chinese patients with invasive fungal infections. Methods Two major single nucleotide polymorphism loci of the CYP2C19 gene (CYP2C19 * 2 and CYP2C19 * 3) were genotyped with PCR and restriction fragment length polymorphism (PCR-RFLP) in 134 patients with invasive fungal infections and 134 healthy volunteers. Allele frequencies and the proportions of metabolizer phenotypes were compared. Results In patients with invasive fungal infections, CYP2C19 * 1, CYP2C19 * 2 and CYP2C19 * 3 alleles showed frequencies of 58.2%, 36.6% and 5.2%. In healthy volunteers, the frequencies of CYP2C19 * 1, CYP2C19 * 2 and CYP2C19 * 3 were 63.4% , 34. 3% and 2. 2%. There was no significant difference in allele frequencies between the two groups. Of the patients with invasive fungal infections, 33. 6% were homozygous extensive metabolizers, 50.0% heterozygous extensive metabolizers and 16.4% poor metabolizers. Of the healthy volunteers, 40.3% were homozygous extensive metabolizers, 48.5% heterozygous extensive metabolizers and 11. 2% poor metabolizers. The proportions of metabolizer phenotypes were similar between the two groups. Conclusions Significant CYP2C19 polymorphism was detected in both groups. Approximately two thirds of the Chinese patients were either heterozygous extensive metabolizers or poor metabolizers. The genetic polymorphism may have important effect on drug metabolism in these patients