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Background  Recently, 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.    Methods  DEX/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 r 2  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.    Results  The 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.    Conclusions  Our 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.

Modulation of cortisol responses to the DEX/CRH test by polymorphisms of the interleukin-1beta gene in healthy adults