Association study of the excitatory amino acid transporter 2 (EAAT2) and glycine transporter 1 (GlyT1) gene polymorphism with schizophrenia in a Polish population
- PMID: 31118638
- PMCID: PMC6499478
- DOI: 10.2147/NDT.S194924
Association study of the excitatory amino acid transporter 2 (EAAT2) and glycine transporter 1 (GlyT1) gene polymorphism with schizophrenia in a Polish population
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.
Keywords: PANSS; excitatory amino acid transporter 2; glutamate system; glycine transporter 1; polymorphism; schizophrenia.
Conflict of interest statement
The authors report no conflicts of interest in this work.
Similar articles
-
Association Study of the SLC1A2 (rs4354668), SLC6A9 (rs2486001), and SLC6A5 (rs2000959) Polymorphisms in Major Depressive Disorder.J Clin Med. 2022 Oct 7;11(19):5914. doi: 10.3390/jcm11195914. J Clin Med. 2022. PMID: 36233781 Free PMC article.
-
Glycine Signaling in the Framework of Dopamine-Glutamate Interaction and Postsynaptic Density. Implications for Treatment-Resistant Schizophrenia.Front Psychiatry. 2020 May 14;11:369. doi: 10.3389/fpsyt.2020.00369. eCollection 2020. Front Psychiatry. 2020. PMID: 32477178 Free PMC article. Review.
-
Polymorphisms in glycine transporter with schizophrenia.Neuropsychopharmacol Hung. 2006 Mar;8(1):17-21. Neuropsychopharmacol Hung. 2006. PMID: 16841561
-
Influence of an interaction between lithium salts and a functional polymorphism in SLC1A2 on the history of illness in bipolar disorder.Mol Diagn Ther. 2012 Oct;16(5):303-9. doi: 10.1007/s40291-012-0004-5. Mol Diagn Ther. 2012. PMID: 23023733
-
Glycine reuptake inhibition as a new therapeutic approach in schizophrenia: focus on the glycine transporter 1 (GlyT1).Curr Pharm Des. 2013;19(7):1311-20. doi: 10.2174/138161213804805766. Curr Pharm Des. 2013. PMID: 23194655 Review.
Cited by
-
Association Study of the SLC1A2 (rs4354668), SLC6A9 (rs2486001), and SLC6A5 (rs2000959) Polymorphisms in Major Depressive Disorder.J Clin Med. 2022 Oct 7;11(19):5914. doi: 10.3390/jcm11195914. J Clin Med. 2022. PMID: 36233781 Free PMC article.
-
Directly and Indirectly _targeting the Glycine Modulatory Site to Modulate NMDA Receptor Function to Address Unmet Medical Needs of Patients With Schizophrenia.Front Psychiatry. 2021 Oct 1;12:742058. doi: 10.3389/fpsyt.2021.742058. eCollection 2021. Front Psychiatry. 2021. PMID: 34658976 Free PMC article. Review.
-
Polymorphism of rs12294045 in EAAT2 gene is potentially associated with schizophrenia in Chinese Han population.BMC Psychiatry. 2022 Mar 8;22(1):171. doi: 10.1186/s12888-022-03799-1. BMC Psychiatry. 2022. PMID: 35260124 Free PMC article.
-
SLC1A2 Gene Polymorphism Influences Methamphetamine-Induced Psychosis.J Pers Med. 2023 Jan 31;13(2):270. doi: 10.3390/jpm13020270. J Pers Med. 2023. PMID: 36836504 Free PMC article.
-
Glycine Signaling in the Framework of Dopamine-Glutamate Interaction and Postsynaptic Density. Implications for Treatment-Resistant Schizophrenia.Front Psychiatry. 2020 May 14;11:369. doi: 10.3389/fpsyt.2020.00369. eCollection 2020. Front Psychiatry. 2020. PMID: 32477178 Free PMC article. Review.
References
-
- Stahl SM. Essential Psychopharmacology. 3rd ed. New York: Cambridge University Press; 2008.
-
- Krystal JH, Perry EB Jr, Gueorguieva R, et al. Comparative and interactive human psychopharmacologic effects of ketamine and amphetamine: implications for glutamatergic and dopaminergic model psychoses and cognitive function. Arch Gen Psychiatry. 2005;62:985–994. doi:10.1001/archpsyc.62.9.985 - DOI - PubMed
LinkOut - more resources
Full Text Sources