Influence of Genetic Polymorphisms Involved in the Hypothalamic-Pituitary-Adrenal Axis and their Interactions with Environmental Factors on Antidepressant Response
Influence of Genetic Polymorphisms Involved in the Hypothalamic-Pituitary-Adrenal Axis and their Interactions with Environmental Factors on Antidepressant Response
复制标题
下丘脑-垂体-肾上腺轴基因多态性及其与环境因素的相互作用对抗抑郁反应的影响
DOI：
10.1111/cns.12201
复制
发表时间：
2014-03-01
影响因子：
5.5
通讯作者：
Zhang, Zhi-Jun
中科院分区：
文献类型：
--
作者：
Geng, Lei-Yu;Ye, Dong-Qing;Zhang, Zhi-Jun
目的探讨HPA轴相关候选基因的遗传多态性及其与环境应激因素在抗抑郁反应中的相互作用。方法对273例中国汉族单相抑郁症患者HPA轴相关候选基因的21个单核苷酸多态性（SNPs）进行抗抑郁治疗8周后抑郁症状缓解的检测。分别采用儿童期创伤量表简表（CTQ-SF）（n=206）和生活事件量表（48项，LES）（n=207）测量儿童期创伤史和近期负性生活事件。报告基因分析被用来评估最显着的SNP对基因express.ResultsA功能多态性在3 ' UTR的促肾上腺皮质激素释放激素受体1（CRHR 1）基因（rs 28364032）和三个单倍型包含它显示了显着的关系与抗抑郁药缓解。进一步基于实验室的基因组研究表明，rs 28364032的G到A的变化导致荧光素酶活性强度降低10-12%。然而，我们没有发现协会的环境和他们的互动与HPA系统相关的基因与抗抑郁药results.ConclusionsOur结果支持CRHR 1在抗抑郁药的药物遗传学的一个明确的作用。这可能导致患者对抗抑郁药物的反应存在差异。
AimsTo investigate the role of genetic polymorphisms in candidate genes associated with the HPA axis and their interactions with environmental stressors in antidepressant response.MethodsThe remission of depressive symptoms after 8weeks of antidepressant treatment was tested against 21 single nucleotide polymorphisms (SNPs) in five candidate genes associated with the HPA axis in a Chinese Han sample suffering from unipolar depression (n=273). Any history of childhood trauma and recent negative life events were measured using the Childhood Trauma Questionnaire-Short Form (CTQ-SF) (n=206) and the Life Event Scale (48 item, LES) (n=207), respectively. Reporter gene assays were used to evaluate the possible effects of the most significant SNP on gene expression.ResultsA functional polymorphism at 3 ' UTR of the corticotropin-releasing hormone receptor 1 (CRHR1) gene (rs28364032) and three haplotypes containing it showed significant relationships with antidepressant remission. Further laboratory-based genomic studies showed that the G-to-A change of rs28364032 resulted in a 10-12% decrease in the intensity of luciferase activity. However, we failed to find association of environments and their interaction with HPA system-related genes with antidepressant remission.ConclusionsOur results support a definite role for CRHR1 in the pharmacogenetics of antidepressant drugs. This may contribute to interpatient differences in their responses to antidepressant drugs.