PRODH rs450046 and proline x COMT Val(158)Met interaction effects on intelligence and startle in adults with 22q11 deletion syndrome

Mariken B. de Koning*, Esther D. A. van Duin, Erik Boot, Oswald J. N. Bloemen, Jaap A. Bakker, Kathryn M. Abel, Therese A. M. J. van Amelsvoort

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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. Here, we explored the association between polymorphisms and full-scale intelligence (FSIQ), startle reactivity (SR) and prepulse inhibition (PPI) in adults with 22q11DS. 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. Thirty-five percent of the subjects were hyperprolinemic with a median proline value of 456 mu mol/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 eta (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 eta (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. 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.
Original languageEnglish
Pages (from-to)3111-3122
Issue number17
Publication statusPublished - Sept 2015


  • 22q11 deletion syndrome
  • Velocardiofacial syndrome
  • Catechol-O-methyl-transferase
  • Proline dehydrogenase
  • Sensorimotor gating

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