细胞色素P2C19检测与消化性溃疡个体化治疗和PPI合理应用

质子泵抑制药(PPI)的抑酸作用是消化性溃疡治疗的基础,既有利于溃疡面愈合,也为抗生素根除幽门螺杆菌创造合适的pH条件;然而相同剂量的PPI对不同患者效果不同。PPI的代谢酶为细胞色素(CY)P2C19酶,由CYP2C19表达产生。在对PPI反应较好的患者中该基因常发生突变,成为CYP2C19*2和CYP2C19*3。由于该突变基因所表达的蛋白质无功能,所以CYP2C19酶整体活性降低,个体对PPI代谢能力减弱,使PPI可作用更长时间。个体依据基因型及PPI代谢的速率可分为纯合快代谢型、杂合快代谢型和慢代谢型。快代谢型消化性溃疡(PU)患者通常需要三联治疗方可治愈,而对于慢代谢型患者通常二联方案即可。同时CYP2C19也影响PPI与其它药物如氯吡格雷间的相互作用。

Detection of CYP2C19 Gene and the Individualized Treatment of Peptic Ulcer or Rational Use of PPI

PPI is the foundation of the treatment of peptic ulcer, which facilitates the healing of ulcer and provides a favorable environment for antibiotics to kill H. pylori. CYP2C19 enzyme, the metabolizer of PPI expressed by CYP2C19 gene, can mutate to CYP2C19^＊2 or CYP2C19^＊3 genes. The enzyme expressed by either of these two genes has as strong activity as CYP2C19 enzyme itself, thus the patients with these mutant genes will leave PPI a longer time to function. Individuals can be classified into mainly three groups： homozygous extensive metabolizer （homoEM）, heterozygous extensive metabolizer （hetEM） and poor metabolizer （PM）. For EM patients, a triple treatment is usually needed, while for PM ones, a bigeminy treatment is always enough. CYP2C19 genotype can also exert an influence on the interaction between PPI and other medicines, like clopidogrel. By gene detection, we can make sure what gene this patient bears and give an effective and economical therapy accordingly. This article summarize the CYP2C19 gene polymorphism and the relationship between cYP2c19 genotype and therapeutic effect on peptic ulcer, the significance of CYP2C19 gene detection for individualized treatment of peptic ulcer and the importance of translation from scientific research to clinical practice.