Association analysis between polymorphisms in the myo-inositol monophosphatase 2 (IMPA2) gene and bipolar disorder.

Abstract

Linkage studies in bipolar disorder (BPD) suggest that a susceptibility locus exists on chromosome 18p11. The myo-inositol monophosphatase 2 gene (IMPA2) maps to this genomic region. Myo-inositol monophosphatase dephosphorylates inositol monophosphate, regenerating free inositol. Lithium, a common treatment for BPD, has been shown to inhibit IMPA2 activity and decrease levels of inositol. It is hypothesized that lithium conveys its therapeutic effect for BPD patients partially through inositol regulation. Hence, dysfunction of inositol caused by IMPA2 irregularity may contribute to the pathophysiology of BPD. In this study, we hypothesize that genetic variations in the IMPA2 gene contributes to increased susceptibility to BPD. We tested this hypothesis by genotyping 9 SNPs (rs1787984; rs585247; rs3974759; rs650727; rs589247; rs669838; rs636173; rs3786285; rs613993) in BPD patients (n=556) and controls (n=735). Genotype and allele frequencies were compared between groups using Chi square contingency analysis. Linkage disequilibrium (LD) between markers was calculated and estimated haplotype frequencies were compared between groups. Single marker analysis revealed several associations between IMPA2 variations and BPD, which were subsequently rendered non-significant after correction for multiple testing. Although our study did not show strong support for an association between the tested IMPA2 polymorphisms and susceptibility to BPD, additional larger studies are necessary to comprehensively investigate a role of the IMPA2 gene in the pathophysiology of BPD.

• Authors: Paul J Bloch, Andrew E Weller, Glenn A Doyle, Thomas N Ferraro, Wade H Berrettini, Rachel Hodge, Falk W Lohoff
• Journal: Progress in neuro-psychopharmacology & biological psychiatry (Prog Neuropsychopharmacol Biol Psychiatry) Vol. 34 Issue 8 Pg. 1515-9 (Dec 01 2010) ISSN: 1878-4216 [Electronic] England
• PMID: 20800640 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• Genetic Markers
• Phosphoric Monoester Hydrolases
• myo-inositol-1 (or 4)-monophosphatase

Topics

• Adult
• Bipolar Disorder (diagnosis, enzymology, genetics)
• Female
• Genetic Markers (genetics)
• Genome-Wide Association Study (methods)
• Haplotypes (genetics)
• Humans
• Male
• Phosphoric Monoester Hydrolases (genetics)
• Polymorphism, Single Nucleotide (genetics)