Abstract
DNA sequence variations within the 22q11 DiGeorge chromosomal region are likely to confer susceptibility to psychotic disorders. In a previous report, we identified several heterozygous alterations, including a complete deletion, of the proline dehydrogenase (PRODH) gene, which were associated with moderate hyperprolinemia in a subset of DSM III schizophrenic patients. Our objective was (i) to determine whether hyperprolinemia is associated with increased susceptibility for any of three psychiatric conditions (schizophrenia, schizoaffective disorder and bipolar disorder) and (ii) to establish a correlation between hyperprolinemia and PRODH genotypes. We have conducted a case–control study including 114 control subjects, 188 patients with schizophrenia, 63 with schizoaffective disorder and 69 with bipolar disorder. We report that, taking into account a confounding effect due to valproate treatment, hyperprolinemia is a risk factor for DSM IIIR schizoaffective disorder (P=0.02, Odds ratio=4.6, 95% confidence interval 1.3–16.3). We did not detect 22q11 interstitial deletions associated with the DiGeorge syndrome among the 320 patients of our sample and we found no association between common PRODH polymorphisms and any of the psychotic disorders. In contrast, we found that five rare PRODH alterations (including a complete PRODH deletion and four missense substitutions) were associated with hyperprolinemia. In several cases, two variations were present simultaneously, either in cis or trans in the same subject. A total of 11 from 30 hyperprolinemic subjects bore at least one genetic variation associated with hyperprolinemia. This study demonstrates that moderate hyperprolinemia is an intermediate phenotype associated with certain forms of psychosis.
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Acknowledgements
HJ was supported by a grant from the Ministère de la Recherche. CD was supported by la Fondation pour la Recherche Medicale. We are indebted to our colleagues who referred patients for this study. We thank the technicians from the Department of Biochemistry for their helpful assistance. We thank R Lalonde and M Martinez for their help. We are grateful to Pr D Valle and Dr HU Bender for communication of unpublished results.
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Jacquet, H., Demily, C., Houy, E. et al. Hyperprolinemia is a risk factor for schizoaffective disorder. Mol Psychiatry 10, 479–485 (2005). https://doi.org/10.1038/sj.mp.4001597
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DOI: https://doi.org/10.1038/sj.mp.4001597
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