Tryptophan metabolism and immunogenetics in major depression: A role for interferon-γ gene
Tryptophan metabolism and immunogenetics in major depression: A role for interferon-γ gene
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DOI：
10.1016/j.bbi.2013.04.003
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发表时间：
2013-07-01
影响因子：
15.1
通讯作者：
Schwarz, Markus J.
中科院分区：
文献类型：
--
作者：
Myint, Aye Mu;Bondy, Brigitta;Schwarz, Markus J.
色氨酸代谢和免疫激活在抑郁症的病理生理过程中发挥作用。促炎细胞因子干扰素-γ转录诱导吲哚胺2，3-双加氧酶，其降解色氨酸并因此诱导血清素消耗。某些细胞因子基因的多态性与抑郁症有关。我们调查了125例抑郁症患者和93例健康对照者干扰素-γ（IFN-γ）基因CA重复多态性、5-羟色胺和色氨酸途径代谢产物谱与临床参数之间的关系。与对照组相比，患者的血清色氨酸和5-羟基吲哚乙酸（5 HIAA）浓度显著较低，血清犬尿氨酸浓度在基线时显著较高（p < 0.0001）。IFN γ CA重复等位基因2纯合子的存在与对照（F = 4.47，p = 0.038）以及患者（F = 3.79，p = 0.045）中较高的犬尿氨酸浓度显著相关。在研究期间，干扰素-γ CA重复等位基因2（纯合子或杂合子）的存在与色氨酸分解随时间的增加显著相关（F = 6.0，p = 0.019）。结果提示IFN γ CA重复等位基因2、色氨酸代谢与药物疗效之间存在相关性。(c)2013 Elsevier Inc. All rights reserved.
The tryptophan metabolism and immune activation play a role in pathophysiology of major depressive disorders. The pro-inflammatory cytokine interferon-gamma transcriptionally induces the indoleamine 2,3-dioxygenase enzyme that degrades the tryptophan and thus induces serotonin depletion. The polymorphism of certain cytokine genes was reported to be associated with major depression. We investigated the association between interferon-gamma (IFN gamma) gene CA repeat polymorphism, the profile of serotonin and tryptophan pathway metabolites and clinical parameters in 125 depressed patients and 93 healthy controls. Compared to controls, serum tryptophan and 5-hydroxyindoleacetic acid (5HIAA) concentrations in the patients were significantly lower and serum kynurenine concentrations were significantly higher at baseline (p < 0.0001). The presence of IFN gamma CA repeat allele 2 homozygous has significant association with higher kynurenine concentrations in controls (F = 4.47, p = 0.038) as well as in patients (F = 3.79, p = 0.045). The existence of interferon-gamma CA repeat allele 2 (homo- or heterozygous) showed significant association with increase of tryptophan breakdown over time during the study period (F = 6.0, p = 0.019). The results indicated the association between IFN gamma CA repeat allele 2, tryptophan metabolism and the effect of medication. (c) 2013 Elsevier Inc. All rights reserved.