河北省汉族精神疾病患者CYP2C19基因多态性与丙戊酸代谢的关系分析

doi:10.3969/j.issn.1006-6233.2023.01.018

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摘要 目的: 通过分析河北省汉族精神疾病患者CYP2C19基因多态性,探讨CYP2C19基因多态性与丙戊酸代谢的关系。方法: 分析464名河北省汉族精神疾病患者CYP2C19的等位基因、基因型及代谢型的分布频率,并比较其在男女分布中的差异。从以上病例中筛选出服用奥氮平和丙戊酸进行治疗的精神分裂症患者52例,采用高效液相色谱串联质谱法检测丙戊酸的血药浓度,采用单因素方差分析比较不同CYP2C19代谢型间丙戊酸血药浓度及单位剂量丙戊酸血药浓度的差异,并应用多因素线性回归分析丙戊酸血药浓度的影响因素。结果: 464名精神疾病患者等位基因 CYP2C19* 1、CYP2C19* 2、CYP2C19* 3、CYP2C19* 17的检出频率依次为:66.60%、27.26%、4.74%、1.40%;共检出的9种基因型,检出频率由高到低依次为:CYP2C19*1/*1、CYP2C19*1/*2、(CYP2C19* 2/* 2、CYP2C19*1/*3)、CYP2C19*1/*17、CYP2C19*2/*3、CYP2C19*3/*3、(CYP2C19*2/*17、CYP2C19*3/*17);超快、快、中间、慢代谢型分布频率分别为 2.37%、42.46%、46.33%、8.84%;等位基因、基因型及代谢型在男女间的分布频率比较,差异无统计学意义(χ²=1.668,P=0.644 ;χ²=13.487,P=0.096;χ²=6.113,P=0.106)。不同代谢型间丙戊酸血药浓度及单位剂量的血药浓度差异均无统计学意义(F=0.146,P=0.864;F=0.006,P=0.994)。线性回归方程为 VPA=43.62+38.03剂量-0.428年龄(F=7.689,P<0.001)。结论: 河北省汉族精神患者的CYP2C19基因具有多态性,其等位基因、基因型及代谢型在男女间的分布差异无统计学意义,CYP2C19的基因多态性未明显影响丙戊酸的代谢。

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关键词 ：丙戊酸, CYP2C19, 基因多态性, 汉族

Abstract：Objective: To analyze the CYP2C19 gene polymorphism and explore the relationship between CYP2C19 gene polymorphism and valproic acid metabolism in Han Chinese patients with mental illness in Hebei Province. Methods: The frequencies of alleles, genotypes and metabolic types of CYP2C19 in 464 Han Chinese patients with mental illness in Hebei Province were analysed, and the differences in men and women were compared separately. Fifty-two patients with schizophrenia treated with olanzapine and valproic acid were selected from the above cases.The blood concentration of valproic acid was determined by high performance liquid chromatography tandem mass spectrometry.One-way ANOVA was used to analyze the differences in valproic acid blood concentrations and blood concentrations per unit dose of valproic acid between different CYP2C19 metabolic types, and multi-factor linear regression was applied to analyze the factors influencing valproic acid blood concentrations. Results: The frequencies of CYP2C19* 1, CYP2C19* 2, CYP2C19* 3 and CYP2C19* 17 in 464 patients with mental illness were 66.60%, 27.26%, 4.74% and 1.40% respectively. A total of 9 genotypes were detected, in descending order of frequency: CYP2C19*1/*1, CYP2C19*1/*2, (CYP2C19* 2/* 2, CYP2C19*1/*3), CYP2C19*1/*17, CYP2C19*2/*3, CYP2C19*3/*3, (CYP2C19*2/*17, CYP2C19*3/*17); the frequencies of distribution of superfast, fast, medium and slow metabolic phenotypes were 2.37%, 42.46%, 46.33% and 8.84%.There was no statistically significant difference in the frequency of distribution of alleles, genotypes and metabolic phenotypes between male and female (χ²=1.668, P=0.644; χ²=13.487, P=0.096; χ²=6.113, P=0.106). Differences in valproic acid blood concentrations between metabolic forms were not statistically significant (F=0.146, P=0.864; F=0.006, P=0.994). The linear regression equation was VPA=43.62 + 38.03 dose - 0.428 age ( F=7.689, P<0.001). Conclusion: The CYP2C19 gene is polymorphic in Han Chinese psychiatric patients in Hebei Province, and the differences in the distribution of alleles, genotypes and metabolic phenotypes between male and female were not statistically significant. Gene polymorphisms of CYP2C19 did not significantly affect the metabolism of valproic acid.

Key words： Valproic acid CYP2C19 Gene polymorphism Han Chinese

基金资助:河北省卫生健康委员会科研基因项目,(编号:20190453)

通讯作者: 刘佳佳

引用本文:

金素丽, 闫会敏, 武艳, 刘同方, 魏从真, 杨雪梅, 赵帅, 刘佳佳. 河北省汉族精神疾病患者CYP2C19基因多态性与丙戊酸代谢的关系分析[J]. 河北医学, 2023, 29(1): 97-102.
JIN Suli, YAN Huimin, WU Yan, et al. Analysis of the Relationship between CYP2C19 Gene Polymorphism and Valproic Acid Metabolism in Han Chinese Patients with Mental Illness in Hebei Province. HeBei Med, 2023, 29(1): 97-102.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2023.01.018 或 http://www.hbyxzzs.cn/CN/Y2023/V29/I1/97

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