title: Association between autism spectrum disorder in individuals with velocardiofacial (22q11.2 deletion) syndrome and PRODH and COMT genotypes.
abstract: Velocardiofacial (VCFS; 22q11.2 deletion) syndrome is a genetic disorder that results from a hemizygous deletion of the q11.2 region on chromosome 22, and is associated with greatly increased risk for psychiatric disorders, including autism spectrum disorder (ASD) and schizophrenia. There is emerging evidence for the involvement of catechol-O-methyltransferase (COMT) and proline dehydrogenase (oxidase) 1 (PRODH) in the psychiatric phenotype of individuals with VCFS. Here, we tested the hypothesis that PRODH and COMT are associated with ASD in youths with VCFS. We found that individuals with VCFS and the low-activity alleles of both PRODH and COMT (rs4819756A and rs4680A) were more likely to present with ASD as compared with individuals with VCFS and the high-activity alleles of these genes [P<0.05; odds ratio=6.0 (95% confidence interval=1.27-28.26; N=87)]. Our results suggest that PRODH and COMT may interact to contribute to the ASD phenotype in individuals with VCFS.
authors.affiliation: Departments of aNeuroscience and Physiology bPsychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse cThe Virtual Center for Velo-Cardio-Facial Syndrome, Manlius dDepartment of Genetics, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Petya D
authors.initials: PD
authors.lastname: Radoeva
authors.forename: Ioana L
authors.initials: IL
authors.lastname: Coman
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Salazar
authors.forename: Karen L
authors.initials: KL
authors.lastname: Gentile
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Higgins
authors.forename: Frank A
authors.initials: FA
authors.lastname: Middleton
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Antshel
authors.forename: Wanda
authors.initials: W
authors.lastname: Fremont
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Shprintzen
authors.forename: Bernice E
authors.initials: BE
authors.lastname: Morrow
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Kates
mesh_terms: D000293:Adolescent; D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22; D004062:DiGeorge Syndrome / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011394:Proline Oxidase / Q000235:genetics*; D055815:Young Adult
chemical_list: D011394:Proline Oxidase; C582834:PRODH protein, human; D002394:Catechol O-Methyltransferase