Influence of genetic polymorphisms involved in the hypothalamic-pituitary-adrenal axis and their interactions with environmental factors on antidepressant response.
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ABSTRACT: 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 (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. RESULTS:A 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. CONCLUSIONS:Our 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.
SUBMITTER: Geng LY
PROVIDER: S-EPMC6493124 | biostudies-literature | 2014 Mar
REPOSITORIES: biostudies-literature
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