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

• Main Authors: Ota Miho, Hattori Kotaro, Teraishi Toshiya, Iijima Yoshimi, Hori Hiroaki, Sasayama Daimei, Fujii Takashi, Higuchi Teruhiko, Amano Naoji, Kunugi Hiroshi
• Format: Article
• Language: English
• Published: BMC 2011-07-01
• Series: Behavioral and Brain Functions
• Online Access: http://www.behavioralandbrainfunctions.com/content/7/1/23

<p>Abstract</p> <p>Background</p> <p>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 (<it>IL-1β</it>) gene has also been reported to be associated with the medication response in depression. These findings prompted us to examine the possible association between <it>IL-1β </it>gene polymorphisms and HPA axis function assessed with the DEX/CRH test.</p> <p>Methods</p> <p>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 <it>IL-1β </it>gene (rs2853550, rs1143634, rs1143633, rs1143630, rs16944) were selected at an r²threshold 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, <it>P </it>values < 0.01 were considered statistically significant for associations between the genotypes and the cortisol levels.</p> <p>Results</p> <p>The cortisol levels after DEX administration (DST-Cortisol) showed significant associations with the genotypes of rs16944 (<it>P </it>= 0.00049) and rs1143633 (<it>P </it>= 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.</p> <p>Conclusions</p> <p>Our results suggest that genetic variations in the <it>IL-1β </it>gene contribute to the HPA axis alteration assessed by DST-Cortisol in healthy subjects. On the other hand, no significant associations of the <it>IL-1β </it>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.</p>