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

• Published in: Psychopharmacology 2015-09, Vol.232 (17), p.3111-3122
• Main Authors: Koning, Mariken B, Duin, Esther DA, Boot, Erik, Bloemen, Oswald JN, Bakker, Jaap A, Abel, Kathryn M, Amelsvoort, Therese AMJ
• Format: Article
• Language: English
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-015-3971-5

Rationale: 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. Objectives: 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 super(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 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 sub(1,43)=7.59; p=0.009; partial eta super(2)=0.15). A significant interaction effect of proline levels and COMT Val super(158)Met genotype was found for SR (F sub(1,16)=7.9; p=0.01; partial eta super(2)=0.33), but not for PPI and FSIQ. In subjects with hyperprolinemia, the COMT Val super(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.