Neureglin 3 gene intronic polymorphisms rs10883866, rs6584400, rs1937970 and rs677221 in patients with Schizophrenia

Background: Schizophrenia is a progressive disease presenting with insufficiencies in thought processes, perceptions, and emotional responsiveness with early onset. There are no laboratory tests or specific biomarkers established so far to diagnose the disease, so clinical and psychiatric analysis are used worldwide. Abnormal neurodevelopment, genetic predisposition and environmental factors are the main factors associated with this disease. The Neuregulin 3 (NRG3) gene encodes the Neuregulin 3 protein which binds to the extracellular domain of ERBB4 receptor tyrosine kinase and controls the proliferation, differentiation, and migration of neural progenitor cells. Methods: Purpose of this study was to find the NRG3 gene polymorphisms i.e., rs10883866, rs6584400, rs1937970 and rs677221 in Schizophrenic patients (n=114) and then compared with healthy controls (n=114). For this purpose, blood samples were taken after the informed consent of patients and the controls followed by DNA extraction and genotyping through PCR-RFLP and PCR-ARMS. Results: The minor allele frequencies of the SNPs rs10883866, rs6584400, rs1937970 and rs677221 in schizophrenic patients were 21.1%, 28.1%, 68.1% and 62.2% respectively. The SNPs rs10883866 and rs6584400 in protective effect toward the Schizophrenia whereas, the other two SNPs showed any statistically significant difference in the allelic distribution between cases and controls. Haplotype block analysis revealed that C-G haplotype in block 1, A-G in block 2 had frequencies of 62.4% and 60.7% in cases. The haplotype G-A in block 1 showed the protective effect towards the disease Schizophrenia with the p-value 0.011. Conclusion: NRG3 has association with the disease schizophrenia. More studies should be conducted including different phenotypic traits of schizophrenia and meticulous clinical evaluation of the patients with larger sample size is suggested to find out the association of NRG3 gene with the schizophrenia.