The Role of Glutamatergic Gene Polymorphisms in the Clinical Phenotypes of Schizophrenia.

BACKGROUND

Personal variations in genetic risk for schizophrenia relate to its phenotypic heterogeneity-both in disorder development and clinical manifestations. Abnormal glutamatergic neurotransmitter system functioning is integrated in the pathogenesis of schizophrenia.

METHODS

A sample of 805 Russian schizophrenia patients from the Siberian Federal region was investigated. We examined the association of 39 single nucleotide polymorphisms in eight genes (, , , , , , , and ) involved in the glutamatergic system with the development of clinical heterogeneity of schizophrenia. The MassARRAY Analyzer 4 was used for genotyping.

RESULTS

rs11644461, rs8057394 and rs7313149 are associated with the continuous type of schizophrenia. The rs8057394G allele is a relative risk factor ( = 0.019) for developing the continuous type of schizophrenia. We found a nominally significant association between negative symptoms of schizophrenia and rs62126236. The rs62126236T allele has a protective effect ( = 0.039) against predominant negative symptoms in schizophrenia. The total Positive and Negative Syndrome Scale (PANSS) scores were significantly associated with rs9788936 after adjusting for multiple testing ( = 0.001).

CONCLUSIONS

In this study the contribution of the glutamatergic gene polymorphisms to the clinical heterogeneity of schizophrenia has been demonstrated.