Genetic association between 5'-upstream single-nucleotide polymorphisms of PDGFRB and schizophrenia in a Korean population.
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.
Kim
Hak-Jae
HJ
Kohwang Medical Research Institute, School of Medicine, Department of Biology, Kyung Hee University, Seoul 130-701, Republic of Korea.
Kim
Min-Ho
MH
Choe
Bong-Keun
BK
Kim
Jong Woo
JW
Park
Jin Kyung
JK
Cho
Ah-Rang
AR
Bae
Hyunsu
H
Shin
Dong-Hun
DH
Yim
Sung Vin
SV
Kwack
KyuBum
K
Kwon
Yunhee Kim
YK
Chung
Joo-Ho
JH
D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007723:Korea; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
D020797:Receptor, Platelet-Derived Growth Factor beta