Dataset Information

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

ACCESS DATA

Publications

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]

PMID: 21693093

Similar Datasets

Project description:HIV-infection is associated with neuroinflammation and greater psychopathological symptoms, which may be mediated by imbalances in the kynurenic pathway (KP). Two key KP enzymes that catabolize kynurenine include kynurenine-aminotransferase II (KATII), which yields antioxidative kynurenine acid [KYNA] in astrocytes, and kynurenine-3-monooxygenase (KMO), which produces neurotoxic metabolites in microglia. The relationships between polymorphisms in KMO and KATII, psychopathological symptoms, and cerebrospinal fluid (CSF) [KYNA] were evaluated in subjects with and without HIV-infection. Seventy-two HIV-positive and 72-seronegative (SN) participants were genotyped for KATII-rs1480544 and KMO-rs1053230. Although our participants were not currently diagnosed with depression or anxiety, they were assessed for psychopathological distress with Center for Epidemiologic Studies-Depression scale and Symptom Checklist-90-Revised. CSF-[KYNA] was also measured in 100 subjects (49 HIV/51 SN). HIV-participants had more psychopathological distress than SN, especially for anxiety. KATII-by-HIV interactions were found on anxiety, interpersonal sensitivity and obsessive compulsivity; KATII-C-carriers had lower scores than TT-carriers in SN but not in HIV. In contrast, the KMO-polymorphism had no influence on psychopathological symptoms in both groups. Overall, CSF-[KYNA] increased with age independently of HIV-serostatus, except KATII-TT-carriers tended to show no age-dependent variations. Therefore, the C-allele in KATII-rs1480544 appears to be protective against psychopathological distress in SN but not in HIV individuals, who had more psychopathological symptoms and likely greater neuroinflammation. The age-dependent increase in CSF-[KYNA] may reflect a compensatory response to age-related inflammation, which may be deficient in KATII-TT-carriers. Targeted treatments that decrease neuroinflammation and increase KYNA in at risk KATII-TT-carriers may reduce psychopathological symptoms in HIV.

Dataset Information

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

Background

Methods

Results

Limitations

Conclusion

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets