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Kynurenine 3-monooxygenase polymorphisms: relevance for kynurenic acid synthesis in patients with schizophrenia and healthy controls.


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.

SUBMITTER: Holtze M 

PROVIDER: S-EPMC3244499 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Kynurenine 3-monooxygenase polymorphisms: relevance for kynurenic acid synthesis in patients with schizophrenia and healthy controls.

Holtze Maria M   Saetre Peter P   Engberg Göran G   Schwieler Lilly L   Werge Thomas T   Andreassen Ole A OA   Hall Håkan H   Terenius Lars L   Agartz Ingrid I   Jönsson Erik G EG   Schalling Martin M   Erhardt Sophie S  

Journal of psychiatry & neuroscience : JPN 20120101 1


<h4>Background</h4>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.<h4>Methods</h4>We analyzed the association between KMO gene polymorphisms and CSF concentrations  ...[more]

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