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

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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-1 beta) 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-1 beta 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-1 beta 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 x 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 x gender interaction. Conclusions: Our results suggest that genetic variations in the IL-1 beta gene contribute to the HPA axis alteration assessed by DST-Cortisol in healthy subjects. On the other hand, no significant associations of the IL-1 beta 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.

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BEHAVIORAL AND BRAIN FUNCTIONS. 7:23 (2011)

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