Hostname: page-component-cd9895bd7-gvvz8 Total loading time: 0 Render date: 2024-12-25T18:45:01.107Z Has data issue: false hasContentIssue false

An association study between polymorphisms in five genes in glutamate and GABA pathway and paranoid schizophrenia

Published online by Cambridge University Press:  16 April 2020

Boyu Zhang
Affiliation:
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), 5, Dong Dan San Tiao, Beijing100005, China National Center of Human Genome Research, Beijing100176, China
Yanbo Yuan
Affiliation:
Peking University Institute of Mental Health, Beijing100083, China
Yanbin Jia
Affiliation:
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), 5, Dong Dan San Tiao, Beijing100005, China National Center of Human Genome Research, Beijing100176, China
Xin Yu
Affiliation:
Peking University Institute of Mental Health, Beijing100083, China
Qi Xu
Affiliation:
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), 5, Dong Dan San Tiao, Beijing100005, China National Center of Human Genome Research, Beijing100176, China
Yucun Shen
Affiliation:
Peking University Institute of Mental Health, Beijing100083, China
Yan Shen*
Affiliation:
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), 5, Dong Dan San Tiao, Beijing100005, China National Center of Human Genome Research, Beijing100176, China
*
*Corresponding author. E-mail address: sheny@ms.imicams.ac.cn (Y. Shen).
Get access

Abstract

Dysfunctions of glutamatergic and GABAergic neurotransmission are two important hypotheses for the pathogenesis of schizophrenia. Thus, genes in the pathway are candidates for schizophrenia susceptibility. Phosphate-activated glutaminase (GLS), glutamine synthetase (GLUL), glutamic acid decarboxylase (GAD), GABA transaminase (ABAT) and succinic semialdehyde dehydrogenase (ALDH5A1) are five primary enzymes in glutamate and GABA synthetic and degradative pathway. In order to investigate the possible involvement of these genes in the development of paranoid schizophrenia, we genotyped 80 paranoid schizophrenics from northern China and 108 matched controls by polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP) methods or directly sequencing of PCR product. Seven SNPs were found to be polymorphic in the population investigated. No significant differences in the genotype distributions or allele frequencies between patients and controls were found. Therefore, we conclude the polymorphisms studied in the five genes do not play major roles in pathogenesis of paranoid schizophrenia in the population investigated.

Type
Original article
Copyright
Copyright © Elsevier SAS 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Akbarian, S, Huntsman, MM, Kim, JJ, Tafazzoli, A, Potkin, SG, Bunney, WE Jr.et al.GABAA receptor subunit gene expression in human prefrontal cortex: comparison of schizophrenics and controls. Cereb Corte 1995;5:550560.CrossRefGoogle ScholarPubMed
Akbarian, S, Kim, JJ, Potkin, SG, Hagman, JO, Tafazzoli, A, Bunney, WE Jr.et al.Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Arch Gen Psychiatr 1995;52:258266.CrossRefGoogle ScholarPubMed
Bird, ED, Spokes, EG, Barnes, J, MacKay, AV, Iversen, LL, Shepherd, MIncreased brain dopamine and reduced glutamic acid decarboxylase and choline acetyl transferase activity in schizophrenia and related psychoses. Lance 1977;2:11571158.CrossRefGoogle ScholarPubMed
Burbaeva, GSH, Boksha, IS, Turishcheva, MS, Vorobyeva, EA, Savushkina, OK, Tereshkina, EBGlutamine synthetase and glutamate dehydrogenase in the prefrontal cortex of patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatr 2003;27:675680.CrossRefGoogle ScholarPubMed
De Luca, V, Muglia, P, Masellis, M, Jane Dalton, E, Wong, GW, Kennedy, JLPolymorphisms in glutamate decarboxylase genes: analysis in schizophrenia. Psychiatr Genet 2004;14:3942.CrossRefGoogle Scholar
Erlander, MG, Tillakaratne, NJ, Feldblum, S, Patel, N, Tobin, AJTwo genes encode distinct glutamate decarboxylases. Neuro 1991;7:91100.Google ScholarPubMed
Gao, XM, Sakai, K, Roberts, RC, Conley, RR, Dean, B, Tamminga, CAIonotropic glutamate receptors and expression of N-methyl-d-aspartate receptor subunits in subregions of human hippocampus: effects of schizophrenia. Am J Psychiatr 2000;157:11411149.CrossRefGoogle ScholarPubMed
Gluck, MR, Thomas, RG, Davis, KL, Haroutunian, VImplications for altered glutamate and GABA metabolism in the dorsolateral prefrontal cortex of aged schizophrenic patients. Am J Psychiatr 2002;159:11651173.CrossRefGoogle ScholarPubMed
Hashimoto, T, Volk, DW, Eggan, SM, Mirnics, K, Pierri, JN, Sun, Zet al.Gene expression deficits in a subclass of GABA neurons in the prefrontal cortex of subjects with schizophrenia. J Neurosci 2003;23:63156326.CrossRefGoogle Scholar
Ibrahim, HM, Hogg, AJ Jr., Healy, DJ, Haroutunian, V, Davis, KL, Meador-Woodruff, JHIonotropic glutamate receptor binding and subunit mRNA expression in thalamic nuclei in schizophrenia. Am J Psychiatr 2000;157:18111823.CrossRefGoogle Scholar
Kobayashi, Y, Kaufman, DL, Tobin, AJGlutamic acid decarboxylase cDNA: nucleotide sequence encoding an enzymatically active fusion protein. J Neurosci 1987;7:27682772.CrossRefGoogle ScholarPubMed
Lappalainen, J, Sanacora, G, Kranzler, HR, Malison, R, Hibbard, ES, Price, LHet al.Mutation screen of the glutamate decarboxylase-67 gene and haplotype association to unipolar depression. Am J Med Genet 2004;124B:8186.CrossRefGoogle ScholarPubMed
Meador-Woodruff, JH, Healy, DJGlutamate receptor expression in schizophrenic brain. Brain Res Brain Res Rev 2000;31:288294.CrossRefGoogle ScholarPubMed
Sherif, F, Eriksson, L, Oreland, LGamma-aminobutyrate aminotransferase activity in brains of schizophrenic patients. J Neural Transm Gen Sect 1992;90:231240.CrossRefGoogle ScholarPubMed
Tamminga, CASchizophrenia and glutamatergic transmission. Crit Rev Neurobiol 1998;12:2136.CrossRefGoogle ScholarPubMed
Volk, DW, Austin, MC, Pierri, JN, Sampson, AR, Lewis, DADecreased glutamic acid decarboxylase67 messenger RNA expression in a subset of prefrontal cortical gamma-aminobutyric acid neurons in subjects with schizophrenia. Arch Gen Psychiatr 2000;57:237245.CrossRefGoogle Scholar
Submit a response

Comments

No Comments have been published for this article.