Additive effect of MTHFR and GRIN1 genetic polymorphisms on the risk of schizophrenia

Schizophrenia is a complex disorder with polygenic inheritance. The MTHFR gene (OMIM: 607093) plays an important role in the folate metabolism. It has been suggested that C677T (rs1801133) and A1298C (rs1801131) genetic polymorphisms in the MTHFR gene lead to the decreased activity of the methylenetetrahydrofolate reductase enzyme which may have significant effect on developing schizophrenia. We used a case-control study to establish the possible association between the C677T and the A1298C polymorphisms and susceptibility to schizophrenia in an Iranian population. The genotypes of the polymorphisms were determined using PCR-RFLP. The data were analyzed by logistic regression model. Data analysis revealed that the combination genotypes of 677CT/1298AA, 677CC/1298CC, 677TT/1298AA, 677CT/1298AC and 677CT/1298CC increase the risk of schizophrenia. In order to evaluate the effect of combined genotypes of the three mentioned polymorphic loci, the frequencies of the compound genotypes were compared between control and patient groups (Table 4). Base on the results, the existence of >4 risk factors showed about 32-fold increased risk for schizophrenia (OR=32.3, 95% CI: 5.52-188, P=<0.001).