title: Modulation of cortisol responses to the DEX/CRH test by polymorphisms of the interleukin-1beta gene in healthy adults.
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.
authors: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan. sasayama@shinshu-u.ac.jp
authors: Daimei
authors: D
authors: Sasayama
authors: Hiroaki
authors: H
authors: Hori
authors: Yoshimi
authors: Y
authors: Iijima
authors: Toshiya
authors: T
authors: Teraishi
authors: Kotaro
authors: K
authors: Hattori
authors: Miho
authors: M
authors: Ota
authors: Takashi
authors: T
authors: Fujii
authors: Teruhiko
authors: T
authors: Higuchi
authors: Naoji
authors: N
authors: Amano
authors: Hiroshi
authors: H
authors: Kunugi
mesh_terms: D000328:Adult; D000483:Alleles; D003346:Corticotropin-Releasing Hormone; D003907:Dexamethasone; D005260:Female; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D053583:Interleukin-1beta / Q000235:genetics* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010912:Pituitary-Adrenal Function Tests / Q000379:methods*; D010913:Pituitary-Adrenal System / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012727:Sex Characteristics
chemical_list: D053583:Interleukin-1beta; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone