Association Analysis for Neuronal Nitric Oxide Synthase Gene Polymorphism with Plasma Nitrite/Nitrate Concentration in Schizophrenia

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Background: Single nucleotide polymorphisms (SNP) of many genes, including the gene for neuronal nitric oxide syn-thase (NOS1), were found significantly associated with schizo-phrenia. According to our previously published results of increased plasma nitric oxide concentration in patients with schizophrenia, we hypothesized that the NOS1 gene polymorphism might be a cause of increased nitric oxide production in patients with schizophrenia and tested the interdependence between plasma nitrite/nitrate concentrations and SNP (a CT transition located in exon 29) of the human NOS1 gene.

Methods: Nitrite/nitrate concentration was measured in blood plasma of 38 patients with schizophrenia and of 39 age and gender matched healthy persons by the colorimet-ric test. The NOS1 gene polymorphism was determined by polymerase chain reaction analysis.

Results: A significantly higher plasma nitrite/nitrate concentration was found in patients with schizophrenia (97.5±33.3 μmol/L, p<0.001) in comparison with controls (61.4±18.9 μmol/L). No T/T genotype was found in healthy individuals and there was a significant difference in the genotype distribution between patients and controls (χ2=24.54, p=0.0000047). Furthermore, a significant difference in the allele frequencies between patients and controls (χ2=19.00, p<0.000013, OR=4.45, 95% CI=2.12–9.39) was noted. Also, a significant difference in plasma nitrite/nitrate concentration was observed between patients having the C/T genotype (99.97±33.83 μmol/L) and the corresponding control (C/T) subgroup (63.88±10.26 μmol/L, p<0.01). However, there were no significant differences in nitrite/nitrate concentration between the patient subgroups with different genotypes (C/C, C/T, T/T).

Conclusions: CT transition located in exon 29 of the human NOS1 gene may be responsible for the increased plasma nitrite/nitrate levels.

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