title: Investigation of variants in the promoter region of PIK3C3 in schizophrenia.
abstract: 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.
authors.affiliation: Bio-X Center, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ruqi
authors.initials: R
authors.lastname: Tang
authors.forename: Xinzhi
authors.initials: X
authors.lastname: Zhao
authors.forename: Chao
authors.initials: C
authors.lastname: Fang
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Ke
authors.initials: K
authors.lastname: Huang
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Huafang
authors.initials: H
authors.lastname: Li
authors.forename: Guoyin
authors.initials: G
authors.lastname: Feng
authors.forename: Shaomin
authors.initials: S
authors.lastname: Zhu
authors.forename: Huijun
authors.initials: H
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Shi
mesh_terms: 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*
chemical_list: D010716:Phosphatidylinositols; D019869:Phosphatidylinositol 3-Kinases