犬尿氨酸 3-单加氧酶多态性：与精神分裂症患者和健康对照者犬尿酸合成的相关性。
Kynurenine 3-monooxygenase polymorphisms: relevance for kynurenic acid synthesis in patients with schizophrenia and healthy controls.
机构信息
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
出版信息
J Psychiatry Neurosci. 2012 Jan;37(1):53-7. doi: 10.1503/jpn.100175.
Abstract
BACKGROUND
Patients with schizophrenia show increased brain and cerebrospinal fluid (CSF) concentrations of the endogenous N-methyl-D-aspartate receptor antagonist kynurenic acid (KYNA). This compound is an end-metabolite of the kynurenine pathway, and its formation indirectly depends on the activity of kynurenine 3-monooxygenase (KMO), the enzyme converting kynurenine to 3-hydroxykynurenine.
METHODS
We analyzed the association between KMO gene polymorphisms and CSF concentrations of KYNA in patients with schizophrenia and healthy controls. Fifteen single nucleotide polymorphisms (SNPs) were selected covering KMO and were analyzed in UNPHASED.
RESULTS
We included 17 patients with schizophrenia and 33 controls in our study. We found an association between a KMO SNP (rs1053230), encoding an amino acid change of potential importance for substrate interaction, and CSF concentrations of KYNA.
LIMITATIONS
Given the limited sample size, the results are tentative until replication.
CONCLUSION
Our results suggest that the nonsynonymous KMO SNP rs1053230 influences CSF concentrations of KYNA.
摘要
背景
精神分裂症患者的大脑和脑脊液（CSF）中内源性 N-甲基-D-天冬氨酸受体拮抗剂犬尿酸（KYNA）浓度升高。该化合物是犬尿氨酸途径的终代谢产物，其形成间接依赖于犬尿氨酸 3-单加氧酶（KMO）的活性，该酶将犬尿氨酸转化为 3-羟基犬尿氨酸。
方法
我们分析了精神分裂症患者和健康对照组中 KMO 基因多态性与 CSF 中 KYNA 浓度之间的关联。选择了覆盖 KMO 的 15 个单核苷酸多态性（SNP），并在 UNPHASED 中进行了分析。
结果
我们在研究中纳入了 17 名精神分裂症患者和 33 名对照者。我们发现 KMO SNP（rs1053230）与 CSF 中 KYNA 浓度之间存在关联，该 SNP 编码一个可能对底物相互作用有重要影响的氨基酸变化。
局限性
鉴于样本量有限，结果尚待复制。
结论
我们的结果表明，非同义 KMO SNP rs1053230 影响 CSF 中 KYNA 的浓度。
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本文引用的文献
1
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Schizophr Bull. 2011 Nov;37(6):1147-56. doi: 10.1093/schbul/sbq112. Epub 2010 Oct 29.
2
Kynurenine 3-monooxygenase (KMO) polymorphisms in schizophrenia: an association study.精神分裂症中犬尿氨酸3-单加氧酶（KMO）基因多态性：一项关联研究。
Schizophr Res. 2011 Apr;127(1-3):270-2. doi: 10.1016/j.schres.2010.10.002. Epub 2010 Oct 27.
3
Increased levels of kynurenine and kynurenic acid in the CSF of patients with schizophrenia.精神分裂症患者脑脊液中犬尿氨酸和犬尿喹啉酸水平升高。
Schizophr Bull. 2012 May;38(3):426-32. doi: 10.1093/schbul/sbq086. Epub 2010 Aug 20.
4
Cortical kynurenine pathway metabolism: a novel target for cognitive enhancement in Schizophrenia.皮质犬尿氨酸途径代谢：精神分裂症认知增强的新靶点。
Schizophr Bull. 2010 Mar;36(2):211-8. doi: 10.1093/schbul/sbq002. Epub 2010 Feb 10.
5
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6
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7
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8
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9
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10
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