Open AccessInfluence of Genetic Polymorphisms Involved in the Hypothalamic–Pituitary–Adrenal Axis and their Interactions with Environmental Factors on Antidepressant Response
Author(s) -
Geng LeiYu,
Ye DongQing,
Shi YanYan,
Xu Zhi,
Pu MengJia,
Li ZanYuan,
Li XiaoLi,
Li Yang,
Zhang ZhiJun
Publication year - 2014
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12201
Subject(s) - antidepressant , single nucleotide polymorphism , ctq tree , haplotype , pharmacogenetics , snp , medicine , polymorphism (computer science) , major depressive disorder , fkbp5 , zolpidem , endocrinology , gene , pharmacology , bioinformatics , oncology , genetics , genotype , glucocorticoid receptor , biology , receptor , poison control , insomnia , injury prevention , environmental health , amygdala , domestic violence , hippocampus
Summary Aims To investigate the role of genetic polymorphisms in candidate genes associated with the HPA axis and their interactions with environmental stressors in antidepressant response. Methods The remission of depressive symptoms after 8 weeks of antidepressant treatment was tested against 21 single nucleotide polymorphisms ( SNP s) 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. Results A functional polymorphism at 3′ UTR of the corticotropin‐releasing hormone receptor 1 ( CRHR 1) 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. Conclusions Our results support a definite role for CRHR 1 in the pharmacogenetics of antidepressant drugs. This may contribute to interpatient differences in their responses to antidepressant drugs.