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

• Published in: Genomics (San Diego, Calif.) Vol. 45; no. 1; pp. 113 - 122
• Main Authors: Sjøholt, Gry, Molven, Anders, Løvlie, Roger, Wilcox, Andrea, Sikela, James M., Steen, Vidar M.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.10.1997
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.1997.4862

Manic–depressive illness is a serious psychiatric disorder that in many, but far from all, patients can be treated with lithium. The main causes for discontinuation of lithium therapy are unpleasant or serious side effects and lack of response. The reason for the striking variation in clinical efficacy of lithium treatment among bipolar patients is not known. The enzymemyo-inositol monophosphatase (IMPase) has been postulated as a target for the mood-stabilizing effects of lithium, but variation in the coding region of the humanIMPAgene encoding IMPase activity has not been observed in manic–depressive patients (Steenet al., Pharmacogenetics,1996, 6, 113–116). It is nevertheless conceivable that polymorphisms or mutations in the noncoding regions of this gene could influence the lithium response in psychiatric patients. As a first step in investigating this possibility, we here report the genomic structure of the humanIMPAgene. The gene is composed of at least nine exons and covers more than 20 kb of sequence on chromosome 8q21.13–q21.3. In the 3′-untranslated part of the gene, we observed a polymorphism (a G to A transition) and also two short sequences similar to the inositol/cholin-responsive element consensus. Finally, we postulate that two additionalIMPA-like transcripts originate from the human genome, one from a position close toIMPAitself on chromosome 8 and the other from chromosome 18p. Our data may contribute to the identification of genetic factors involved in the pathogenesis and determination of treatment response in manic–depressive illness.