Genetic association between 5'-upstream single-nucleotide polymorphisms of PDGFRB and schizophrenia in a Korean population.
Schizophr Res
; 103(1-3): 201-8, 2008 Aug.
Article
en En
| MEDLINE
| ID: mdl-18541413
PDGFRB is located on chromosome 5q31-q32, a chromosomal region identified by linkage analyses to contain a susceptibility gene for schizophrenia (SCZ). Recent research has focused on the role of the N-methyl-d-aspartate (NMDA) receptor in the pathogenesis of SCZ. D4 dopamine receptor-mediated transactivation of the gene encoding platelet-derived growth factor receptor beta (PDGFRB) has immediate effects on synaptic neurotransmission via calcium-dependent inactivation of NMDA receptors. In this study, we investigate the association between the PDGFRB gene and SCZ in a Korean population. We screened 6 single-nucleotide polymorphisms (SNPs) in the 5'-upstream region of PDGFRB and conducted a case-control study of 381 SCZ patients and 752 controls. The genotype and haplotype frequencies of 3 of the 6 SNPs [SNP1 (g.-1924T>C, rs3756314), SNP3 (g.-1772A>G, rs3756312) and SNP4 (rs3756311, g.-1658G>A)] were significantly associated with SCZ [SNP1, corrected p=0.012 (co-dominant model), 0.002 (Dominant model), and 0.506 (Recessive model); SNP3 and 4, corrected p=0.003, 0.009, and 0.049]. Haplotype analysis also revealed that ht1 (CGG) and ht2 (TAA) were significantly associated with SCZ (ht1, corrected p=0.018, 0.340, and 0.010; ht2, corrected p=0.002, 0.009, and 0.016). Transient transfection in neuronal cells revealed that ht1 had higher luciferase activity than the vector alone. Furthermore, Pdgfrb expression was increased in the frontal cortex and hippocampus in a mouse model of SCZ induced by MK801. We conclude that SNPs of the 5'-upstream region of PDGFRB are associated with SCZ in a Korean population. These are weak positives that require future studies to confirm these results.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Esquizofrenia
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Receptor beta de Factor de Crecimiento Derivado de Plaquetas
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Polimorfismo de Nucleótido Simple
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Animals
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
Asia
Idioma:
En
Revista:
Schizophr Res
Asunto de la revista:
PSIQUIATRIA
Año:
2008
Tipo del documento:
Article
Pais de publicación:
Países Bajos