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

Behav Brain Funct. 2011 Jul 5;7:23. doi: 10.1186/1744-9081-7-23.

Abstract

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 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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Corticotropin-Releasing Hormone*
  • Dexamethasone*
  • Female
  • Genotype
  • Humans
  • Hydrocortisone / metabolism*
  • Hypothalamo-Hypophyseal System / physiology
  • Interleukin-1beta / genetics*
  • Interleukin-1beta / physiology
  • Male
  • Middle Aged
  • Pituitary-Adrenal Function Tests / methods*
  • Pituitary-Adrenal System / physiology
  • Polymorphism, Single Nucleotide / genetics*
  • Sex Characteristics

Substances

  • Interleukin-1beta
  • Dexamethasone
  • Corticotropin-Releasing Hormone
  • Hydrocortisone