title: Hyperprolinemia is a risk factor for schizoaffective disorder.
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.
authors.affiliation: Inserm U614, IFRMP, Faculté de Médecine, Rouen 76183, France.
authors.forename: H
authors.initials: H
authors.lastname: Jacquet
authors.forename: C
authors.initials: C
authors.lastname: Demily
authors.forename: E
authors.initials: E
authors.lastname: Houy
authors.forename: B
authors.initials: B
authors.lastname: Hecketsweiler
authors.forename: J
authors.initials: J
authors.lastname: Bou
authors.forename: G
authors.initials: G
authors.lastname: Raux
authors.forename: J
authors.initials: J
authors.lastname: Lerond
authors.forename: G
authors.initials: G
authors.lastname: Allio
authors.forename: S
authors.initials: S
authors.lastname: Haouzir
authors.forename: A
authors.initials: A
authors.lastname: Tillaux
authors.forename: C
authors.initials: C
authors.lastname: Bellegou
authors.forename: G
authors.initials: G
authors.lastname: Fouldrin
authors.forename: P
authors.initials: P
authors.lastname: Delamillieure
authors.forename: J F
authors.initials: JF
authors.lastname: Ménard
authors.forename: S
authors.initials: S
authors.lastname: Dollfus
authors.forename: T
authors.initials: T
authors.lastname: D'Amato
authors.forename: M
authors.initials: M
authors.lastname: Petit
authors.forename: F
authors.initials: F
authors.lastname: Thibaut
authors.forename: T
authors.initials: T
authors.lastname: Frébourg
authors.forename: D
authors.initials: D
authors.lastname: Campion
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D018692:Antimanic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D016022:Case-Control Studies; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D010641:Phenotype; D011392:Proline / Q000097:blood* / Q000187:drug effects; D011394:Proline Oxidase / Q000187:drug effects / Q000235:genetics*; D011618:Psychotic Disorders / Q000097:blood / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D012016:Reference Values; D012307:Risk Factors; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D012737:Sex Factors; D018709:Statistics, Nonparametric; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D018692:Antimanic Agents; D014635:Valproic Acid; D011392:Proline; D011394:Proline Oxidase