The kynurenine pathway in major depression: Haplotype analysis of three related functional candidate genes
The kynurenine pathway in major depression: Haplotype analysis of three related functional candidate genes
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DOI：
10.1016/j.psychres.2011.03.012
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发表时间：
2011-08-15
影响因子：
11.3
通讯作者：
Rothermundt, Matthias
中科院分区：
文献类型：
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作者：
Claes, Stephan;Myint, Aye-Mu;Rothermundt, Matthias
在重度抑郁症（MDD）的研究中，一个一致的发现是免疫系统功能障碍。在这方面的相关代谢途径之一是犬尿氨酸途径。在重度抑郁症患者中，该通路的神经保护臂和神经毒性臂之间存在不平衡，血浆尿酸浓度较低。因此，我们研究了参与这种代谢的三种酶的三个候选基因的单核苷酸多态性（SNP）和单倍型关联。对338例（266例重度抑郁症和72例双相抑郁症）不相关的重度抑郁症高加索患者和310例年龄、性别和种族匹配的对照进行了色氨酸羟化酶2 （TPH2）、犬尿氨酸3单加氧酶（KMO）和犬尿氨酸氨基转移酶3 (KAT III) snp和单倍型关联分析。在使用PLINK对KAT III的单倍型进行滑动窗口分析时，包括第一个SNP （rs12729558）的所有窗口中，重度抑郁发作患者和对照组的总体单倍型分布（OMNIBUS）在所有窗口中都有显著差异，p值范围在1.75 x 10 = 5和0.006之间。这是由于单倍型CGCTCT（参考6个SNP窗口分析），在约5.7%的患者和1.9%的健康对照中发现。这是由于CGCTCT单倍型，该单倍型在双相患者和重度抑郁症患者中的频率均显著高于对照人群（p < 0.001）。KAT III基因CGCTCT的单倍型可能影响该酶在一些重性抑郁发作患者中形成犬尿酸的功能。2011爱思唯尔爱尔兰有限公司版权所有。
A consistent finding in major depressive disorder (MDD) research is dysfunction of the immune system. One of the relevant metabolic pathways in this regard is the kynurenine pathway. In patients with major depression, an imbalance between neuroprotective and neurotoxic arms of the pathway with lower plasma kynurenic acid concentration was demonstrated. Therefore, we investigated Single Nucleotide Polymorphism (SNP) and haplotype association of three candidate genes of the three enzymes involved in this metabolism. The three genes, namely, tryptophan hydroxylase 2 (TPH2), kynurenine 3 monooxygenase (KMO) and kynurenine amino transferase 3 (KAT III) SNPs and haplotype association analysis was performed in 338 (266 major depression and 72 bipolar depression) unrelated Caucasian patients with major depressive episodes and 310 age, gender and ethnicity matched controls. In sliding window analyses using PLINK of the haplotypes of KAT III, all windows which include the first SNP (rs12729558), the overall haplotype distribution (OMNIBUS) was significantly different between patients with a major depressive episode and control for all windows, with p-values ranging between 1.75 x 10 = 5 and 0.006. This is due to the haplotype CGCTCT (referring to 6 SNP window analysis), which is found in about 5.7% of patients and 1.9% of healthy controls. It was due to CGCTCT haplotype and the frequencies of this haplotype in both bipolar patients and patients with major depression showed significantly higher than the control population (p < 0.001). This haplotype of KAT III gene CGCTCT may have effect on the function of this enzyme in formation of kynurenic acid in some patients with major depressive episodes. (C) 2011 Elsevier Ireland Ltd. All rights reserved.