title: Evidence for association of DNA sequence variants in the phosphatidylinositol-4-phosphate 5-kinase IIalpha gene (PIP5K2A) with schizophrenia.
abstract: Linkage studies in schizophrenia have identified a candidate region on chromosome 10p14-11 as reported for several independent samples. We investigated association of DNA sequence variants in a plausible candidate gene located in this region, the gene for phosphatidylinositol-4-phosphate 5-kinase IIalpha (PIP5K2A), in a sample of 65 sib-pair families for which linkage had been reported. Evidence for association was obtained for 15 polymorphisms spanning 73.6 kb in the genomic region of the gene between intron 4 and the 3' untranslated region, a region with high degree of linkage disequilibrium. Single nucleotide polymorphism (SNP) rs10828317 located in exon 7 and causing a non-synonymous amino-acid exchange (asparagine/serine) produced a P-value of 0.001 (experiment-wide significance level 0.00275) for over-transmission of the major allele coding for serine, analysed by transmission disequilibrium test using FAMHAP. Association of this SNP with schizophrenia has been also described in a sample of 273 Dutch schizophrenic patients and 580 controls (P=0.0004). PIP5K2A is involved in the biosynthesis of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), one of the key metabolic crossroads in phosphoinositide signalling. PI(4,5)P2 plays a role in membrane transduction of neurotransmitter signals as well as in intracellular signalling, pathways that may be impaired in schizophrenia.
authors.affiliation: Western Australian Institute of Medical Research and Center for Medical Research, University of Western Australia, Perth, WA, Australia.
authors.forename: S G
authors.initials: SG
authors.lastname: Schwab
authors.forename: M
authors.initials: M
authors.lastname: Knapp
authors.forename: P
authors.initials: P
authors.lastname: Sklar
authors.forename: G N
authors.initials: GN
authors.lastname: Eckstein
authors.forename: C
authors.initials: C
authors.lastname: Sewekow
authors.forename: M
authors.initials: M
authors.lastname: Borrmann-Hassenbach
authors.forename: M
authors.initials: M
authors.lastname: Albus
authors.forename: T
authors.initials: T
authors.lastname: Becker
authors.forename: J F
authors.initials: JF
authors.lastname: Hallmayer
authors.forename: B
authors.initials: B
authors.lastname: Lerer
authors.forename: W
authors.initials: W
authors.lastname: Maier
authors.forename: D B
authors.initials: DB
authors.lastname: Wildenauer
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D005091:Exons; D005190:Family; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007438:Introns; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012559:Schizophrenia / Q000201:enzymology / Q000235:genetics*; D035781:Siblings
chemical_list: D004247:DNA; C514871:PIP4K2A protein, human; D017853:Phosphotransferases (Alcohol Group Acceptor)