Investigation of variants in the promoter region of PIK3C3 in schizophrenia.
The PIK3C3 gene has been implicated as a candidate gene for schizophrenia by functional evidence and genetic association studies. A series of previous studies have found susceptibility SNPs in promoter region. To further verify its susceptibility to schizophrenia in the Chinese population and the function of the polymorphisms, we performed a case control study in 556 unrelated schizophrenia patients and 563 normal controls as well as an in vitro functional analysis. In our association analysis of-432C-/T, we discovered obvious differences in allele frequency between patients and controls (P=0.017). A T/C haplotype constructed by -432C-/T and -86insC, which are tightly linked with each other (r(2)=1) can significantly weaken promoter's transcriptional activity by 20% (p=0.002 by t-test). Though we cannot exclude the possibility that susceptibility of -432C-/T is caused by its linkage disequilibrium with other causal variants, our results do support PIK3C3 play a significant role in the etiology of schizophrenia.
Tang
Ruqi
R
Bio-X Center, Shanghai Jiao Tong University, Shanghai, China.
Zhao
Xinzhi
X
Fang
Chao
C
Tang
Wei
W
Huang
Ke
K
Wang
Lei
L
Li
Huafang
H
Feng
Guoyin
G
Zhu
Shaomin
S
Liu
Huijun
H
He
Lin
L
Shi
Yongyong
Y
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D010716:Phosphatidylinositols / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000201:enzymology* / Q000235:genetics*
D010716:Phosphatidylinositols; D019869:Phosphatidylinositol 3-Kinases