An investigation of the dihydropyrimidinase-like 2 (DPYSL2) gene in schizophrenia: genetic association study and expression analysis.
Several linkage studies support a susceptibility locus for schizophrenia on chromosome 8p21-22. In this study, we investigated a gene mapping to 8p21, dihydropyrimidinase-like 2 (DPYSL2). DPYSL2 plays an important role in axonal formation and dysfunction of DPYSL2 may result in neurodevelopmental abnormalities. In previous studies, the expression of the gene has been shown to display alteration in the brain of schizophrenia patients compared with those of healthy controls. Recently, Nakata and colleagues found polymorphisms in the 3'-end of DPYSL2 to be associated with schizophrenia, especially the paranoid type, in a Japanese population. In this study, we genotyped four SNPs in DPYSL2 in 2552 Chinese Han specimens. Case-control and TDT analyses were performed to detect association of DPYSL2 with schizophrenia. However, no allele, genotype or haplotype association was found. We investigated the expression of DPYSL2 in 29 schizophrenia patients and 54 healthy controls using quantitative real-time PCR and no difference was found between the two groups. In a comparative allele-specific expression test, we used two SNPs as markers. Only a small proportion of heterozygotes revealed a significant difference (>20%) in allele representation. The results indicated the mRNA level did not contribute mainly in the altered expression of the gene in schizophrenia patients. Although our results provided no evidence for DPYSL2 itself as a susceptibility gene for schizophrenia, recent findings have indicated that DPYSL2 may interact with other candidate genes for schizophrenia and be worthy of further studies.
Zhao
Xinzhi
X
Bio-X Center, Shanghai Jiao Tong University, Shanghai, China.
Tang
Ruqi
R
Xiao
Zeping
Z
Shi
Yongyong
Y
Feng
Guoying
G
Gu
Niufan
N
Shi
Jianguo
J
Xing
Yangling
Y
Yan
Lijuan
L
Sang
Hong
H
Zhu
Shaomin
S
Liu
Huijun
H
Chen
Wuyan
W
Liu
Jixia
J
Tang
Wei
W
Zhang
Jing
J
He
Lin
L
D000328:Adult; D000483:Alleles; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics*
D018076:DNA, Complementary; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C095114:collapsin response mediator protein-2; D012313:RNA