Genomic Structure and Chromosomal Localization of a Humanmyo-Inositol Monophosphatase Gene (IMPA)

Sjøholt, Gry; Molven, Anders; Løvlie, Roger; Wilcox, Andrea S.; Sikela, James M.; Steen, Vidar M.

doi:10.1006/geno.1997.4862

Cited by 41 publications

(34 citation statements)

References 31 publications

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“…Three of the promoter variants (À241_À237dup, À207T4C and À185A4G) are present in a region of alternative transcription start sites, 12,13 where À241_À237dup represents the five first nucleotides of the transcript reported by Yoshikawa et al 29 The À207T4C polymorphism is localized in a putative MZF1 regulatory site. 28 There is some evidence for altered IMPase enzyme activity 21 and changes in the IMPA2 expression levels 23 in bipolar patients compared to control individuals.…”

Section: Impa2mentioning

confidence: 95%

“…12 The GC-rich exon 1 and promoter region was amplified as a 1142 bp PCR fragment with the following primers: A101, forward (5 0 -GAGCCTCAGTTTCCTCATCTGT-CT-3 0 ) and A102, reverse (5 0 -CAGGGCAGCTCCGGA-TAAC-3 0 ).…”

Section: Polymorphism Scanningmentioning

confidence: 99%

“…13-21.3. 12 Recently, a gene on chromosome 18p11.2, named IMPA2, was predicted to encode an IMPase of high similarity to the IMPA1-encoded protein, especially in the active site and the ion-binding regions. 12,13 However, the IMPA2-encoded protein has not yet been isolated or functionally characterized.…”

Section: Introductionmentioning

confidence: 99%

“…12,20,[27][28][29] In this study, we aimed to further investigate the possible role of the two IMPaseencoding genes in bipolar disorder. An initial scanning for additional variations in IMPA1 and IMPA2 was performed in a limited number of Norwegian manic-depressive patients and normal controls, followed by a family-based association study using a sample of bipolar Palestinian Arab families.…”

Section: Introductionmentioning

confidence: 99%

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Examination of IMPA1 and IMPA2 genes in manic-depressive patients: association between IMPA2 promoter polymorphisms and bipolar disorder

et al. 2003

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Manic-depressive (bipolar) illness is a serious psychiatric disorder with a strong genetic predisposition. The disorder is likely to be multifactorial and etiologically complex, and the causes of genetic susceptibility have been difficult to unveil. Lithium therapy is a widely used pharmacological treatment of manic-depressive illness, which both stabilizes the ongoing episodes and prevents relapses. A putative target of lithium treatment has been the inhibition of the myo-inositol monophosphatase (IMPase) enzyme, which dephosphorylates myo-inositol monophosphate in the phosphatidylinositol signaling system. Two genes encoding human IMPases have so far been isolated, namely myo-inositol monophosphatase 1 (IMPA1) on chromosome 8q21.13-21.3 and myo-inositol monophosphatase 2 (IMPA2) on chromosome 18p11.2. In the present study, we have scanned for DNA variants in the human IMPA1 and IMPA2 genes in a pilot sample of Norwegian manic-depressive patients, followed by examination of selected polymorphisms and haplotypes in a family-based bipolar sample of Palestinian Arab proband-parent trios. Intriguingly, two frequent single-nucleotide polymorphisms (À461C4T and À207T4C) in the IMPA2 promoter sequence and their corresponding haplotypes showed transmission disequilibrium in the Palestinian Arab trios. No association was found between the IMPA1 polymorphisms and bipolar disorder, neither with respect to disease susceptibility nor with variation in lithium treatment response. The association between manic-depressive illness and IMPA2 variants supports several reports on the linkage of bipolar disorder to chromosome 18p11.2, and sustains the possible role of IMPA2 as a susceptibility gene in bipolar disorder.

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Section: Impa2mentioning

confidence: 95%

Section: Polymorphism Scanningmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Examination of IMPA1 and IMPA2 genes in manic-depressive patients: association between IMPA2 promoter polymorphisms and bipolar disorder

et al. 2003

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“…11,12 The gene is a potential biochemical target for the action of lithium. 13 Linkage studies 14,15 have suggested the presence of a susceptibility locus for bipolar disorder on chromosome 18p11.2. The gene has been screened for polymorphisms and tested for association with BP 11,12 and schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

Association study of myo-inositol monophosphatase 2 (IMPA2) polymorphisms with bipolar affective disorder and response to lithium treatment

et al. 2004

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Lithium is the most effective mood-stabilizing drug in the therapy of bipolar affective disorder (BP). It is thought to exert its effect via the phosphatidylinositol signalling system. Myo-inositol monophosphatase 2 (IMPA2) codes for an enzyme in this system that is inhibited by lithium. It is located on 18p11.2, a region implicated as a BP susceptibility locus. We examined eight single-nucleotide polymorphisms (SNPs) identified within this gene for association with BP, using 237 parents-offspring trios and in 174 cases and 170 controls. No SNP showed association with BP. When good responders to lithium treatment were compared with the poor responders, some statistically significant differences emerged for two SNPs; however, the sample became too small to draw definitive conclusions. We cannot find support for the involvement of variation in IMPA2 in susceptibility to bipolar disorder, but the role of this and other genes from the phosphoinositol signalling pathway in predicting response to lithium treatment merits further investigation.

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Abnormalities of Inositol Metabolism in Lymphocytes as Biomarkers for Bipolar Disorder

Agam

Bersudsky²,

Belmaker³

2009

The Handbook of Neuropsychiatric Biomarkers, Endophenotypes and Genes

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Genomic Structure and Chromosomal Localization of a Humanmyo-Inositol Monophosphatase Gene (IMPA)

Cited by 41 publications

References 31 publications

Examination of IMPA1 and IMPA2 genes in manic-depressive patients: association between IMPA2 promoter polymorphisms and bipolar disorder

Examination of IMPA1 and IMPA2 genes in manic-depressive patients: association between IMPA2 promoter polymorphisms and bipolar disorder

Association study of myo-inositol monophosphatase 2 (IMPA2) polymorphisms with bipolar affective disorder and response to lithium treatment

Abnormalities of Inositol Metabolism in Lymphocytes as Biomarkers for Bipolar Disorder

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