CYP2C19基因多态性对精神分裂症患者丙戊酸血药浓度的影响

Effect of CYP2C19 Genetic Polymorphism on Blood Concentration of Valproic Acid in Schizophrenia

目的研究CYP2C19基因多态性与精神分裂症患者心境稳定剂丙戊酸血药浓度的关系。方法选择奥氮平治疗且服用丙戊酸钠作为心境稳定剂的精神分裂症患者160例,采集血液,测定CYP2C19基因型以及丙戊酸血药浓度,比较各个基因型血药浓度的差异。结果 *2/*2型(122.06±41.30)mg·L?1和*2/*3型(132.34±51.34)mg·L?1患者丙戊酸血药浓度明显高于野生*1/*1型(79.41±25.14)mg·L?1(P<0.05或P<0.01);*1/*1、*1/*2和*1/*3型之间、*2/*2和*2/*3型之间血药浓度无统计学差异;PM型血药浓度(122.13±42.85)mg·L?1与EM型(80.59±48.60)mg·L?1比较,显著升高(P<0.05)。结论*2/*2和*2/*3型CYP2C19患者,其血液丙戊酸浓度较高,该类患者服用丙戊酸作为精神分裂症心境稳定剂时,宜适当降低用药剂量。

OBJECTIVE To study the relationship between CYP2C19 genetic polymorphism and blood concentration of mood stabilizer of valproic acid in schizophrenia patients. METHODS Schizophrenia patients treated with olanzapine and mood stabilizer of valproic acid were recruited based on the criteria of inclusion and exclusion. The blood samples were collected for the determinations of CYP2C19 genetic polymorphism and blood concentration of valproic acid. Then the blood concentration of valproic acid within the types of CYP2C19 genetic polymorphism was compared. RESULTS Blood concentration of valproic acid in the types of ＊2/＊2（122.06±41.30）mg·L^-1 and ＊2/＊3（132.34±51.34）mg·L^-1 were obviously higher than that of the wild ＊1/＊1 type（79.41±25.14）mg·L^-1（P0.05, P0.01）. However, it was not significantly different in the types of ＊1/＊1, ＊1/＊2 and ＊1/＊3 or in the types of ＊2/＊2 and ＊2/＊3. PM type（122.13±42.85）mg·L^-1 had obviously higher blood concentration than EM type（80.59±48.60）mg·L^-1（P0.05）. CONCLUSION The CYP2C19 types of ＊2/＊2 and ＊2/＊3 had high blood concentrations of valproic acid. These patients should receive a low dose of mood stabilizer of valproic acid in the treatment of schizophrenia.