Abstract
Background: Excitatory amino acid transporter 2 encoded by SLC1A2 is responsible for approximately 90% of glutamate uptake. Glycine transporter 1, encoded by SLC6A9, is responsible for maintaining a low concentration of the N-methyl-D-aspartate receptor (NMDAR) co-agonist - glycine in the synaptic cleft, suggesting its participation in the development of the NMDARs hypofunction described in schizophrenia. Aim: The aim of this study was to evaluate whether the functional polymorphism-181 A/C (rs4354668) of the SLC1A2 and the rs2486001 (IVS3+411 G/A) in the SLC6A9 are involved in schizophrenia development and its clinical picture in the Polish population. Methods: The study group consisted of 393 unrelated Caucasian patients (157 [39.9%] females and 236 [60.1%] males; mean age 41±12) diagnosed with schizophrenia according to the DSM-5, and 462 healthy controls. The results of the Positive and Negative Syndrome Scale (PANSS) were presented in the five-dimensional model. Polymorphisms of SLC1A2 and SLC6A9 were genotyped with the use of PCR-RFLP assay. Results: There were no statistically significant differences in the frequency of genotypes and alleles between the patients and controls for SLC1A2 and SLC6A9 polymorphisms in either the entire sample or after stratification according to gender. In the haplotype analysis, men with CA haplotype had more than 1.5 higher risk to develop schizophrenia than women (OR=1.63 [95% CI=1.17-2.27, p<0.05]). The influence of gender, genotypes of both analyzed polymorphisms and gender x genotype interactions on individual dimensions of the PANSS scale has not been observed. Also, there was no association of either polymorphism with suicide attempts. Conclusion: The results of the present study did not indicate an association of polymorphism-181 A/C (rs4354668) in SLC1A2 and rs2486001 in SLC6A9 with onset of schizophrenia and its psychopathology in a Polish population.