Polymorphism Screening of PIP5K2A: A Candidate Gene for Chromosome 10p-Linked Psychiatric Disorders

Pavla Stopkova, Takuya Saito, Cathy S J Fann, Demitri F. Papolos, Jan Vevera, Ivo Paclt, Ilja Zukov, Rafael Stryjer, Rael D. Strous, Herbert M. Lachman

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Lithium is a potent noncompetitive inhibitor of inositol monophosphatases, enzymes involved in phosphoinositide (PI) and inositol phosphate metabolism. A critical component of the PI pathway is phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), which is hydrolyzed to second messengers and has a direct role in synaptic vesicle function. Interestingly, a number of genes involved in the synthesis and dephosphorylation of PtdIns(4,5)P2 are found in regions of the genome previously mapped in bipolar disorder (BD) including 10p12, 21q22, and 22q11, among others. Some of these regions overlap with loci mapped in schizophrenia (SZ). One gene involved in PI metabolism that maps to a region of interest is 10p12-linked PIP5K2A, a member of the phosphatidylinositol 4-phosphate 5-kinase family. Polymorphism screening revealed the existence of an imperfect CT repeat polymorphism located near the exon 9-intron 9 splice donor site. A modest difference was found in the distribution of alleles from this highly polymorphic variant when bipolar and schizophrenic subjects were compared with controls; relatively rare short repeat variants were found more commonly in patients and homozygosity for a common long repeat variant was found more commonly in controls. These data suggest that the imperfect CT repeat in PIP5K2A intron 9 should be further investigated as a possible candidate allele for 10p12-linked psychiatric disorders.

Original languageEnglish (US)
Pages (from-to)50-58
Number of pages9
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume123 B
Issue number1
StatePublished - Nov 15 2003

Fingerprint

Phosphatidylinositols
Psychiatry
Chromosomes
Phosphatidylinositol 4,5-Diphosphate
Introns
Genes
Alleles
RNA Splice Sites
Inositol Phosphates
Synaptic Vesicles
Second Messenger Systems
Bipolar Disorder
Lithium
Exons
Schizophrenia
Genome
Enzymes

Keywords

  • Candidate gene
  • Endocytosis
  • Exocytosis
  • PIP2
  • Synaptic vesicle

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)

Cite this

Polymorphism Screening of PIP5K2A : A Candidate Gene for Chromosome 10p-Linked Psychiatric Disorders. / Stopkova, Pavla; Saito, Takuya; Fann, Cathy S J; Papolos, Demitri F.; Vevera, Jan; Paclt, Ivo; Zukov, Ilja; Stryjer, Rafael; Strous, Rael D.; Lachman, Herbert M.

In: American Journal of Medical Genetics - Neuropsychiatric Genetics, Vol. 123 B, No. 1, 15.11.2003, p. 50-58.

Research output: Contribution to journalArticle

Stopkova, P, Saito, T, Fann, CSJ, Papolos, DF, Vevera, J, Paclt, I, Zukov, I, Stryjer, R, Strous, RD & Lachman, HM 2003, 'Polymorphism Screening of PIP5K2A: A Candidate Gene for Chromosome 10p-Linked Psychiatric Disorders', American Journal of Medical Genetics - Neuropsychiatric Genetics, vol. 123 B, no. 1, pp. 50-58.
Stopkova, Pavla ; Saito, Takuya ; Fann, Cathy S J ; Papolos, Demitri F. ; Vevera, Jan ; Paclt, Ivo ; Zukov, Ilja ; Stryjer, Rafael ; Strous, Rael D. ; Lachman, Herbert M. / Polymorphism Screening of PIP5K2A : A Candidate Gene for Chromosome 10p-Linked Psychiatric Disorders. In: American Journal of Medical Genetics - Neuropsychiatric Genetics. 2003 ; Vol. 123 B, No. 1. pp. 50-58.
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