中国汉族血液病患者CYP2C19基因多态性对伏立康唑初始稳态谷浓度的影响

Effect of CYP2C19 genetic polymorphisms on initial steady-state voriconazole trough concentration in Chinese hematological patients

目的研究CYP2C19基因多态性及生理病理等临床非遗传因素对伏立康唑在中国汉族血液病患者体内初始稳态血浆谷浓度[(C_(ss))_(min)]的影响。方法采用高效液相色谱法(HPLC)检测患者体内(C_(ss))_(min),飞行时间质谱法(MALDI-TOF MS)对rs4244285、rs498689和rs12248560三个位点进行基因检测。采用非参数检验、Spearman秩相关检验及多重线性回归等统计学方法研究CYP2C19基因多态性及临床非遗传因素对(C_(ss))_(min)的影响。结果共纳入了78名患者,(C_(ss))_(min)变异系数达64.9%。CYP2C19基因多态性、年龄是造成(C_(ss))_(min)个体间差异的影响因素,其中中间代谢型(IMs)及弱代谢型(PMs)患者较快代谢型(EMs)患者表现出更高的(C_(ss))_(min),IMs及PMs患者之间的(C_(ss))_(min)差异无统计学意义(P>0.05);年龄与(C_(ss))_(min)呈正相关。结论本研究为早期制定VRC个体化给药方案提供了临床依据,以达到提高VRC抗真菌疗效和促进患者预后的目的。

Objective The aim of this research was to study the effects of CYP2C19 genetic polymorphisms and physiological or pathological non-genetic factors on initial steady - state voriconazole trough concentration [ （ CSS ） min ] in Hart hematological patients. Methods The concentrations were measured by a validated HPLC method. The genotypes were detected by MALDI - TOF MS （ MassARRAY system） , three SNPs （rs4244285, rs498689 and rs12248560） were genotyped in this study. Spearman rank test was used to study correlations between quantitative data, and non - parametric test was used to perform comparisons between groups. A muhiple linear regression model was used to identify the determinants contributing to the variability of （CSS）min. Results A total of 78 patients were enrolled in the study. The coefficient of variation of （ Css ） min was 64. 9%. It was identified that genetic polymorphisms of CYP2C19 and age showed effects on （ CSS ）min. Intermediate metabolizers （IMs） and poor metabolizers （PMs） patients showed higher （CSS）min ; However, no difference was found between IMs patients and PMs patients （ P 〉 0. 05 ） . Besides, there was positive correlation between （CSS）mln and age. Conclusion The study will be conducive to clinical early individualized medication of vorieonazole and it is essential for curative effect of antifungal treatment and prognosis.