CYP1A2基因多态性与度洛西汀抗抑郁临床效应的关系

发布时间：2018-06-04 02:37

本文选题：CYP1A2 + 基因多态性　；参考：《郑州大学》2014年硕士论文

【摘要】：目的 1.研究河南地区汉族人群抑郁症患者CYP1A2基因C734A及G-2964A位点的多态性分布。 2.研究CYP1A2基因C734A及G-2964A位点多态性与度洛西汀治疗抑郁症的临床疗效和不良反应的关系。方法 1.研究对象223例河南地区汉族抑郁症患者，均符合《中国精神疾病分类与诊断标准第3版》抑郁发作的诊断标准，汉密尔顿抑郁量表（17项）≥17分，年龄18~60岁。 2.基因型检测采用聚合酶链反应扩增和限制性片段长度多态性技术,分析CYP1A2基因C734A及G-2964A位点的基因多态性,然后根据基因型检测结果将受试者分为3种代谢型。 3.临床效应评价用度洛西汀（60mg/d）对223例受试者进行为期6周的抗抑郁治疗,用汉密尔顿抑郁量表评定度洛西汀的临床疗效，副反应量表评定度洛西汀所致不良反应。 4.统计学分析使用Hardy-Winberg平衡检验样本的群体代表性，基因型与临床疗效的关系采用方差分析，基因型与不良反应的关系采用χ2检验。结果 1河南地区汉族抑郁症患者CYP1A2基因C734A及G-2964A位点多态性共223例受试者中，C734A位点C/C、C/A和A/A基因型频率分别为13.90％、45.74％和40.36％；G-2964A位点G/G、G/A、A/A基因型频率分别为54.71％、36.32％、8.97％。 2不同基因型或代谢型之间度洛西汀临床疗效的比较共220例受试者完成为期6周的抗抑郁治疗。 2.1CYP1A2/C734A不同基因型间HAMD减分率的比较：治疗6周末，HAMD减分率3组之间总体比较差异具有统计学意义（p0.01），其中C/C组与C/A组相比差异无统计学意义（p0.05），2组分别与A/A组相比均差异有统计学意义（均p0.01）。 2.2CYP1A2/G-2964A不同基因型间HAMD减分率的比较：治疗6周末,HAMD减分率3组之间总体比较差异有统计学意义（p0.01），其中G/A组与A/A组相比差异无统计学意义（p0.05），2组分别与G/G组相比均差异有统计学意义（均p0.01）。 2.3不同代谢型间HAMD减分率的比较：治疗6周末，3组之间HAMD减分率总体比较差异有统计学意义（p0.01），两两比较均差异有统计学意义（均p0.01）。 3不同基因型或代谢型之间度洛西汀所致不良反应的比较 223例受试者中，3例受试者在治疗早期因严重不良反应脱落，均计入不良反应发生组。 3.1CYP1A2/C734A不同基因型间不良反应的比较：3组基因型患者不良反应发生率总体比较差异有统计学意义（P0.01），其中C/C组与C/A组相比差异无统计学意义（p0.05），2组分别与A/A组相比均差异具有统计学意（p0.05、p0.01）。 3.2CYP1A2/G-2964A不同基因型间不良反应的比较：3组基因型患者不良反应发生率总体比较差异有统计学意义（P0.01），其中G/A组与A/A组相比差异无统计学意义（p0.05），2组与G/G组相比均差异有统计学意义（均P0.01）。 3.3不同代谢型间不良反应的比较：3组基因型患者不良反应发生率总体比较差异有统计学意义（P0.05），，两两比较差异均具有统计学意义（均p0.05）；结论 1.河南地区汉族抑郁症患者与长沙地区汉族健康人群之间在CYP1A2/C734A位点的多态性分布无明显差异，而两者在CYP1A2/G-2964A位点的多态性分布有一定差异。 2. CYP1A2基因C734A及G-2964A位点多态性可影响度洛西汀治疗抑郁症的临床疗效和不良反应。
[Abstract]:objective
1. to study the polymorphisms of CYP1A2 gene C734A and G-2964A loci in patients with depression in Henan Han population.
2. to study the relationship between the polymorphism of C734A and G-2964A locus of CYP1A2 gene and the clinical efficacy and adverse reactions of duloxetine in the treatment of depression.
Method
1. the 223 cases of Han depression in Henan area were all in accordance with the criteria for the classification and diagnosis of Chinese mental diseases and the diagnostic standard third for depression, and the Hamilton Depression Scale (17) was more than 17, and the age was 18~60 years.
2. genotypes were detected by polymerase chain reaction amplification and restriction fragment length polymorphism, and the gene polymorphism of C734A and G-2964A loci of CYP1A2 gene was analyzed. Then the subjects were divided into 3 metabolic types according to the results of genotypic detection.
3. 60mg/d was used for a 6 week antidepressant treatment of 223 subjects. The Hamilton depression scale was used to evaluate the clinical efficacy of duloxetine, and the side reaction scale was used to assess the adverse effects of luoxetine.
4. statistical analysis used the group representativeness of the Hardy-Winberg balance test sample. The relationship between genotypes and clinical efficacy was analyzed by variance analysis. The relationship between genotype and adverse reaction was tested by chi 2 test.
Result
1 among 223 subjects with CYP1A2 gene C734A and G-2964A polymorphism in the Henan Han depression, the frequencies of C734A loci C/C, C/A and A/A genotypes were 13.90%, 45.74% and 40.36%, respectively, and G-2964A loci G/G, G/A, and A/A genotype frequencies were 54.71%, 36.32%, and 8.97%..
2 the clinical efficacy of duloxetine between different genotypes or metabolites was 220. The subjects completed 6 weeks of antidepressant treatment.
The comparison of the reduction rate of HAMD among different genotypes of 2.1CYP1A2/C734A: the total difference between the 3 groups of the HAMD reduction rate in the 6 weekend was statistically significant (P0.01), and there was no statistical difference between the C/C group and the C/A group (P0.05), and the difference between the 2 groups was statistically significant compared with the A/A group (all P0.01).
The comparison of the reduction rate of HAMD among different genotypes of 2.2CYP1A2/G-2964A: the total difference between the 3 groups of the HAMD reduction rate in the 6 weekend was statistically significant (P0.01), and there was no statistical difference between the G/A group and the A/A group (P0.05), and the difference between the 2 groups was statistically significant compared with the G/G group (all P0.01).
2.3 the comparison of the reduction rate of HAMD between different metabolic types: the total difference of HAMD reduction rate among the 3 groups was statistically significant (P0.01), and the difference of 22 was statistically significant (P0.01).
3 Comparison of adverse reactions induced by duloxetine between different genotypes or metabolic types
Of the 223 subjects, 3 of the subjects fell off due to serious adverse reactions at the early stage of treatment, and all of them were included in the group of adverse reactions.
The comparison of the adverse reactions among different genotypes in 3.1CYP1A2/C734A: there was a significant difference in the incidence of adverse reactions between the 3 groups of genotypes (P0.01), and there was no significant difference between the group C/C and the C/A group (P0.05), and the differences in the 2 groups were all compared with the A/A group (P0.05, P0.01).
The comparison of the adverse reactions among different genotypes of 3.2CYP1A2/G-2964A: the incidence of adverse reactions in the 3 groups was statistically significant (P0.01), and there was no significant difference between the group G/A and the A/A group (P0.05), and the difference between the 2 groups was statistically significant compared with the G/G group (P0.01).
3.3 comparison of the adverse reactions among different metabolic types: there was a significant difference in the incidence of adverse reactions between the 3 groups (P0.05), and 22 of the differences were statistically significant (P0.05).
conclusion
1. there is no significant difference in the polymorphism distribution of the CYP1A2/C734A loci between the Han people with depression in Henan and the healthy people of the Han nationality in Changsha, but there are some differences in the polymorphism distribution at the CYP1A2/G-2964A loci.
2. the polymorphism of CYP1A2 gene C734A and G-2964A can affect the clinical efficacy and side effects of duloxetine in the treatment of depression.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R96

【参考文献】