Prodynorphin gene polymorphisms in schizophrenia: An association study

Background: Family, adoption and twin studies support genetic component to pathogenesis of schizophrenia. Prodynorphin is one of the endogenous opiate precursors. Its products are neuromodulators that influence a variety of neurological functions including behavior. In addition some of their direct and indirect pharmacological action supports their role a candidate genes in schizophrenia. Objective: To conduct a systematic search of the prodynorphin gene for polymorphisms and mutations in schizophrenia patients and case controls and to correlate these with any association with this complex disorder. Method: Patient and control samples were collected by standard methods. Diagnosis was made using DSM-IV criteria after abstraction from extensive clinical records. Systematic search of entire gene for variations was done using Bi-directional fingerprinting method in the patients and controls. This was confirmed by sequencing. Results and Conclusions: We report several polymorphisms in the prodynorphin gene. One of these is a single nucleotide polymorphism in the promoter region that seems to increase the risk of developing schizophrenia two fold. The significance of these findings needs to be further elucidated.