Kynurenine 3-monooxygenase Polymorphisms: Relevance for Kynurenic Acid Synthesis in Patients with Schizophrenia and Healthy Controls

Overview

Journal J Psychiatry Neurosci

Specialty Psychiatry

Date 2011 Jun 23

PMID 21693093

Citations 46

Authors

Maria Holtze

Peter Saetre

Goran Engberg

Lilly Schwieler

Thomas Werge

Ole A Andreassen

Hakan Hall

Lars Terenius

Ingrid Agartz

Erik G Jonsson

Martin Schalling

Sophie Erhardt

Affiliations

Soon will be listed here.

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.

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