Abstract
BackgroundRecently, hypothalamus-pituitary-adrenal (HPA) axis function assessed with the combined dexamethasone (DEX)/corticotropin releasing hormone (CRH) test has been shown to be associated with response to antidepressant treatment. A polymorphism (rs16944) in the interleukin-1beta (IL-1β) gene has also been reported to be associated with the medication response in depression. These findings prompted us to examine the possible association between IL-1β gene polymorphisms and HPA axis function assessed with the DEX/CRH test.MethodsDEX/CRH test was performed in 179 healthy volunteers (45 males: mean age 40.5 ± 15.8 years; 134 females: mean age 47.1 ± 13.2 years). Five tagging single nucleotide polymorphisms (SNPs) of IL-1β gene (rs2853550, rs1143634, rs1143633, rs1143630, rs16944) were selected at an r2 threshold of 0.80 with a minor allele frequency > 0.1. Genotyping was performed by the TaqMan allelic discrimination assay. A two-way factorial analysis of variance (ANOVA) was performed with the DEX/CRH test results as the dependent variable and genotype and gender as independent variables. To account for multiple testing, P values < 0.01 were considered statistically significant for associations between the genotypes and the cortisol levels.ResultsThe cortisol levels after DEX administration (DST-Cortisol) showed significant associations with the genotypes of rs16944 (P = 0.00049) and rs1143633 (P = 0.0060), with no significant gender effect or genotype × gender interaction. On the other hand, cortisol levels after CRH administration (DEX/CRH-Cortisol) were affected by gender but were not significantly influenced by the genotype of the examined SNPs, with no significant genotype × gender interaction.ConclusionsOur results suggest that genetic variations in the IL-1β gene contribute to the HPA axis alteration assessed by DST-Cortisol in healthy subjects. On the other hand, no significant associations of the IL-1β gene polymorphisms with the DEX/CRH-Cortisol were observed. Confirmation of our findings in futures studies may add new insight into the communication between the immune system and the HPA axis.
Highlights
Hypothalamus-pituitary-adrenal (HPA) axis function assessed with the combined dexamethasone (DEX)/corticotropin releasing hormone (CRH) test has been shown to be associated with response to antidepressant treatment
No significant allelic or genotypic differences have been found between patients with depression and healthy controls [10,11,12], three studies have consistently shown that the G allele of rs16944 in the IL-1b gene is associated with poor response to antidepressant treatment [10,13,14]
Two studies have reported the influence of genetic polymorphisms on DEX suppression test (DST) [43,44], one of which has shown that an allele in a polymorphism within the CRHBP gene, which regulates the CRH system, was associated with pronounced DEX suppression of corticotropin and with nonresponse to citalopram treatment in depressed subjects [43]
Summary
Hypothalamus-pituitary-adrenal (HPA) axis function assessed with the combined dexamethasone (DEX)/corticotropin releasing hormone (CRH) test has been shown to be associated with response to antidepressant treatment. No significant allelic or genotypic differences have been found between patients with depression and healthy controls [10,11,12], three studies have consistently shown that the G allele of rs16944 in the IL-1b gene is associated with poor response to antidepressant treatment [10,13,14]. This evidence suggests that genetic regulation of inflammatory processes mediated by IL-1b is involved in the pathophysiology of depression and resistance to antidepressant treatment
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