广西壮族和汉族精神分裂症患者 CYP2C19 基因变异及其与丙戊酸血浆浓度关系的评估

Pharmacogenomics and Personalized Medicine Pub Date : 2024-05-14 DOI:10.2147/pgpm.s457805

Jun Mei Teng, Shuiqing Qin, Danyu Lu, Yefa Gu, Shi Jie Tang, Qiong Yan, Jiawei Yao, Chao Zhang

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摘要

目的：调查广西壮族和汉族精神分裂症患者CYP2C19基因型分布和等位基因频率，研究精神分裂症患者CYP2C19基因变异与丙戊酸（VPA）标准化血药浓度的相关性，评估年龄、性别和体重指数（BMI）对VPA标准化血药浓度的影响：2022 年 2 月至 12 月间，对 192 名接受 VPA 治疗的壮族和汉族精神分裂症患者进行了研究。采用均相酶联免疫法测定稳态VPA浓度，并通过q-PCR测定CYP2C19 &ast1、&ast2和&ast3位点。采用卡方检验比较了南宁壮族和汉族的 CYP2C19 基因型分布，并与其他民族进行了对比。非参数检验分析了VPA的变化，通过多元逐步回归确定了关键因素：研究发现了&ast2和&ast3位点上的5种CYP2C19基因型，其中&ast3/&ast3基因型在两个队列中均不存在。CYP2C19 在广西壮族和汉族中的分布与回族和哈萨克族有明显差异。在 192 名受试者中，不同代谢类型和 18-60 岁年龄组的 VPA 血液水平保持一致，但性别差异很大。多变量分析显示，性别和体重指数是重要的影响因素，盖过了CYP2C19基因型和年龄的影响：结论：在广西，壮族和汉族精神分裂症患者的CYP2C19基因变异显示出统计学上无差异的等位基因和代谢分布。性别和体重指数会影响精神分裂症患者的标准VPA血药浓度。然而，在我们的研究队列中，CYP2C19基因型和年龄并不是VPA标准化血药浓度的主要决定因素：CYP2C19基因丙戊酸血液药物浓度壮族汉族

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Evaluation of CYP2C19 Genetic Variant and Its Lack of Association with Valproic Acid Plasma Concentrations Among Zhuang and Han Schizophrenia Patients in Guangxi

Purpose: To investigate the CYP2C19 genotype distribution and allelic frequency among the Zhuang and Han schizophrenic populations in Guangxi, examine the correlation between CYP2C19 genetic variants and standardized blood levels of Valproic Acid (VPA) in schizophrenic patients, and evaluate the effects of age, gender, and Body Mass Index (BMI) on standardized VPA blood concentrations.
Patients and Methods: Between February and December 2022, 192 Zhuang and Han schizophrenia patients treated with VPA were studied. Steady-state VPA concentrations were determined using homogeneous enzyme immunoassays, and CYP2C19 &ast1, &ast2, and &ast3 loci via q-PCR. CYP2C19 genotype distributions between Zhuang and Han groups in Nanning were compared using chi-square tests and contrasted with other ethnicities. Non-parametric tests analyzed VPA variations, identifying critical factors through multivariate stepwise regression.
Results: The study identified five CYP2C19 genotypes at the &ast2 and &ast3 loci, with the &ast3/&ast3 genotype absent in both cohorts. The CYP2C19 distribution in Guangxi Zhuang and Han mirrors, yet diverges significantly from Hui and Kazakh groups. Among 192 subjects, VPA blood levels remained consistent across metabolic types and ages 18– 60 but varied significantly by gender. Multivariate analysis revealed gender and BMI as significant factors, overshadowing CYP2C19 genotype and age.
Conclusion: In Guangxi, CYP2C19 genetic variants in Zhuang and Han schizophrenia patients demonstrate statistically indistinguishable allelic and metabolic distributions. Gender and BMI can influence standardized VPA blood concentrations in schizophrenia patients. However, in our study cohort, the CYP2C19 genotype and age are not the primary determinants of standardized VPA blood levels.

Keywords: CYP2C19 gene, valproic acid, blood drug concentration, Zhuang Chinese, Han Chinese

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Pharmacogenomics and Personalized Medicine

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