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.

journal_name

Mol Psychiatry

journal_title

Molecular psychiatry

authors

Schwab SG,Knapp M,Sklar P,Eckstein GN,Sewekow C,Borrmann-Hassenbach M,Albus M,Becker T,Hallmayer JF,Lerer B,Maier W,Wildenauer DB

doi

10.1038/sj.mp.4001864

subject

Has Abstract

pub_date

2006-09-01 00:00:00

pages

837-46

issue

9

eissn

1359-4184

issn

1476-5578

pii

4001864

journal_volume

11

pub_type

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