Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
Behav Brain Funct. 2011 Jul 5;7:23. doi: 10.1186/1744-9081-7-23.
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.
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.
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.
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.
最近，使用联合地塞米松（DEX）/促肾上腺皮质激素释放激素（CRH）测试评估的下丘脑-垂体-肾上腺（HPA）轴功能与抗抑郁治疗反应有关。白细胞介素-1β（IL-1β）基因中的一个多态性（rs16944）也被报道与抑郁症的药物反应有关。这些发现促使我们研究 IL-1β 基因多态性与 DEX/CRH 测试评估的 HPA 轴功能之间的可能关联。
在 179 名健康志愿者（45 名男性：平均年龄 40.5 ± 15.8 岁；134 名女性：平均年龄 47.1 ± 13.2 岁）中进行 DEX/CRH 测试。选择 IL-1β 基因的五个标记单核苷酸多态性（SNP）（rs2853550、rs1143634、rs1143633、rs1143630、rs16944），其次要等位基因频率>0.1，r2 阈值为 0.80。通过 TaqMan 等位基因鉴别分析进行基因分型。将 DEX/CRH 测试结果作为因变量，基因型和性别作为自变量，进行双因素方差分析（ANOVA）。为了考虑多次检验，将 P 值<0.01 视为基因型与皮质醇水平之间关联的统计学意义。
DEX 给药后（DST-Cortisol）的皮质醇水平与 rs16944（P=0.00049）和 rs1143633（P=0.0060）的基因型显著相关，而性别无显著影响或基因型×性别无显著相互作用。另一方面，CRH 给药后（DEX/CRH-Cortisol）的皮质醇水平受性别影响，但受所检查 SNP 的基因型影响不显著，且基因型×性别无显著相互作用。
我们的结果表明，IL-1β 基因的遗传变异导致健康受试者 DST-Cortisol 评估的 HPA 轴改变。另一方面，IL-1β 基因多态性与 DEX/CRH-Cortisol 无显著关联。在未来的研究中确认我们的发现可能会为免疫系统和 HPA 轴之间的通信增加新的见解。
