Modulation of cortisol responses to the DEX/CRH test by polymorphisms of the interleukin-1beta gene in healthy adults.
Modulation of cortisol responses to the DEX/CRH test by polymorphisms of the interleukin-1beta gene in healthy adults.
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DOI：
10.1186/1744-9081-7-23
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发表时间：
2011-07-05
期刊：
影响因子：
--
通讯作者：
Kunugi H
中科院分区：
文献类型：
--
作者：
Sasayama D;Hori H;Iijima Y;Teraishi T;Hattori K;Ota M;Fujii T;Higuchi T;Amano N;Kunugi H
最近，用地塞米松（DEX）/促肾上腺皮质激素释放激素（CRH）联合试验评估下丘脑-垂体-肾上腺（HPA）轴功能已被证明与抗抑郁药治疗的反应有关。白细胞介素-1 β（IL-1β）基因的多态性（rs 16944）也被报道与抑郁症的药物反应相关。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试验。在r2阈值为0.80的条件下，选择IL-1β基因的5个标签单核苷酸多态性位点（rs 2853550、rs 1143634、rs 1143633、rs 1143630、rs 16944），次要等位基因频率> 0.1。通过TaqMan等位基因辨别测定进行基因分型。以DEX/CRH试验结果为因变量，基因型和性别为自变量，进行双因素方差分析（ANOVA）。为了解释多重检验，P值< 0.01被认为是基因型和皮质醇水平之间的关联具有统计学显著性。DEX给药后皮质醇水平（DST-皮质醇）与rs 16944（P = 0.00049）和rs 1143633（P = 0.0060）基因型显著相关，无显著性别效应或基因型×性别交互作用。另一方面，CRH给药后的皮质醇水平（DEX/CRH-Cortisol）受性别影响，但不受所检测SNP基因型的显著影响，无显著基因型×性别相互作用。我们的研究结果表明，IL-1β基因的遗传变异有助于通过DST-皮质醇评估健康受试者的HPA轴改变。另一方面，未观察到IL-1β基因多态性与DEX/CRH-Cortisol的显著关联。在未来的研究中证实我们的发现可能会增加对免疫系统和HPA轴之间通信的新见解。
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.
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DOI：
10.1016/s0162-3109(00)00199-5
发表时间：
2000-07-20
期刊：
IMMUNOPHARMACOLOGY
影响因子：
--
作者：
Jeon, YJ;Han, SH;Kim, HM
通讯作者：
Kim, HM
影响因子：
--
作者：
Binder, Elisabeth B.;Owens, Michael J.;Nemeroff, Charles B.
通讯作者：
Nemeroff, Charles B.
影响因子：
3.7
作者：
Binder, E. B.;Kuenzel, H. E.;Holsboer, F.
通讯作者：
Holsboer, F.
影响因子：
4.2
作者：
HEUSER, IJ;GOTTHARDT, U;HOLSBOER, F
通讯作者：
HOLSBOER, F
影响因子：
4.8
作者：
Horia, Hiroaki;Ozeki, Yuji;Kunugi, Hiroshi
通讯作者：
Kunugi, Hiroshi