Abstract

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. © 2008 Elsevier B.V. All rights reserved.

Author keywords

Platelet-derived growth factor receptor beta; Promoter; Schizophrenia; Single-nucleotide polymorphism; Transfection

Indexed keywords

EMTREE drug terms: dizocilpine; luciferase; platelet derived growth factor beta receptor

EMTREE medical terms: 5' untranslated region; adult; animal experiment; animal model; article; case control study; controlled study; enzyme activity; female; frontal cortex; genetic association; genetic transfection; genotype; haplotype; hippocampus; human; Korea; major clinical study; male; mouse; nonhuman; priority journal; protein expression; schizophrenia; single nucleotide polymorphism

MeSH: Adult; Animals; Case-Control Studies; Chromosomes, Human, Pair 5; Disease Models, Animal; Female; Frontal Lobe; Gene Frequency; Genetic Predisposition to Disease; Genotype; Haplotypes; Hippocampus; Humans; Korea; Male; Mice; Mice, Inbred ICR; Middle Aged; Polymorphism, Single Nucleotide; Receptor, Platelet-Derived Growth Factor beta; Schizophrenia
Medline is the source for the MeSH terms of this document.

Chemicals and CAS Registry Numbers: dizocilpine, 77086-21-6;Receptor, Platelet-Derived Growth Factor beta, EC 2.7.1.112