title: PRODH rs450046 and proline x COMT Val¹⁵⁸ Met interaction effects on intelligence and startle in adults with 22q11 deletion syndrome.
abstract: BACKGROUND
  22q11 deletion syndrome (22q11DS) is associated with an increased risk for psychotic disorders, suggesting a relationship between genotypes and the pathophysiology of psychotic disorders. Two genes in the deleted region, catechol-O-methyl-transferase (COMT) and proline dehydrogenase (oxidase) 1 (PRODH), contain polymorphisms associated with neuropsychiatric phenotypes.
  
  
  OBJECTIVE
  Here, we explored the association between polymorphisms and full-scale intelligence (FSIQ), startle reactivity (SR) and prepulse inhibition (PPI) in adults with 22q11DS.
  
  
  METHODS
  Forty-five adults with 22q11DS were genotyped for PRODH rs450046, rs372055 and COMT Val(158)Met. Plasma proline levels, FSIQ, SR and PPI were measured.
  
  
  RESULTS
  Thirty-five percent of the subjects were hyperprolinemic with a median proline value of 456 μmol/L. C allele carriers of PRODH rs450046 had a lower FSIQ compared to T allele carriers, indicating the C allele to be a risk allele (C allele: mean FSIQ 60.2 (sd 8.7); T allele: mean FSIQ 73.7 (sd 11.5); F 1,43 = 7.59; p = 0.009; partial η (2) = 0.15). A significant interaction effect of proline levels and COMT Val(158)Met genotype was found for SR (F 1,16 = 7.9; p = 0.01; partial η (2) = 0.33), but not for PPI and FSIQ. In subjects with hyperprolinemia, the COMT Val(158)Met genotype effect on SR was stronger than in subjects with normal proline levels.
  
  
  CONCLUSIONS
  Overall, these data provide further evidence for the risk effect of elevated proline levels combined with the COMT Met allele and support the possibilities of using 22q11DS as a model to investigate genotype effects on psychiatric disorders.
authors.affiliation: Arkin Mental Health Care, Baron G.A. Tindalstraat 27, 1019 TS, Amsterdam, The Netherlands, mariken.dekoning@planet.nl.
authors.forename: Mariken B
authors.initials: MB
authors.lastname: de Koning
authors.forename: Esther D A
authors.initials: ED
authors.lastname: van Duin
authors.forename: Erik
authors.initials: E
authors.lastname: Boot
authors.forename: Oswald J N
authors.initials: OJ
authors.lastname: Bloemen
authors.forename: Jaap A
authors.initials: JA
authors.lastname: Bakker
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Abel
authors.forename: Thérèse A M J
authors.initials: TA
authors.lastname: van Amelsvoort
mesh_terms: D058165:22q11 Deletion Syndrome / Q000235:genetics* / Q000523:psychology*; D000328:Adult; D015415:Biomarkers; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007360:Intelligence / Q000235:genetics*; D007361:Intelligence Tests; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011392:Proline / Q000097:blood; D011394:Proline Oxidase / Q000235:genetics*; D011619:Psychotropic Drugs / Q000627:therapeutic use; D013216:Reflex, Startle / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics; D055815:Young Adult
chemical_list: D015415:Biomarkers; D011619:Psychotropic Drugs; D011392:Proline; D011394:Proline Oxidase; C582834:PRODH protein, human; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase