title: The human protein kinase C gamma gene (PRKCG) as a susceptibility locus for behavioral disinhibition.
abstract: This study explores the association between a highly heritable behavioral disinhibition phenotype and the protein kinase C gamma (PRKCG) gene in an ethnically diverse youth sample from Colorado, USA. The rationale for this study was based on the impulsive behavior and increased ethanol consumption observed in the protein kinase C gamma (PKC-gamma)-deficient mouse model. Two composite behavioral disinhibition phenotypes and their component behavioral scores [conduct disorder, attention-deficit hyperactivity disorder (ADHD), substance experimentation (SUB) and novelty-seeking] were examined for association with five independent PRKCG single nucleotide polymorphisms (SNPs). Association analysis for the five individual SNPs revealed modest genetic association of Exon 14 (rs2242244) and Upstream (rs307941) markers with the behavioral disinhibition composite variables in the combined, Hispanic and African-American samples. Additionally, haplotype-based association analysis for two SNPs located in Intron 3 (rs402691) and Exon 6 (rs3745406) indicated a significant overall association of the PRKCG locus with the ADHD-hyperactive subscale scores in the combined and Caucasian samples, supporting the relation between impulsive behaviors and the PRKCG gene. A significant haplotype association was also observed with SUB scores but only in the Hispanic ethnic group, highlighting the marker variability for each ethnic group. In conclusion, our results support the role of the PKC-gamma enzyme in behavioral impulsivity previously observed in mice. This study provides the first exploration of the PRKCG gene and its association with behavioral disinhibition and warrants further study in other larger population samples.
authors.affiliation: Institute for Behavioral Genetics, University of Colorado, Boulder, USA, and Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA. Isabel.Schlaepfer@colorado.edu
authors.forename: Isabel R
authors.initials: IR
authors.lastname: Schlaepfer
authors.forename: Hilary V
authors.initials: HV
authors.lastname: Clegg
authors.forename: Robin P
authors.initials: RP
authors.lastname: Corley
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Crowley
authors.forename: John K
authors.initials: JK
authors.lastname: Hewitt
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Hopfer
authors.forename: Kenneth
authors.initials: K
authors.lastname: Krauter
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lessem
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Rhee
authors.forename: Michael C
authors.initials: MC
authors.lastname: Stallings
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Wehner
authors.forename: Susan E
authors.initials: SE
authors.lastname: Young
authors.forename: Marissa A
authors.initials: MA
authors.lastname: Ehringer
mesh_terms: D000293:Adolescent; D000328:Adult; D000987:Antisocial Personality Disorder / Q000208:ethnology / Q000235:genetics; D001289:Attention Deficit Disorder with Hyperactivity / Q000208:ethnology / Q000235:genetics; D044383:Black People / Q000235:genetics; D002874:Chromosome Mapping; D019955:Conduct Disorder / Q000208:ethnology / Q000235:genetics*; D005106:Exploratory Behavior; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D007175:Impulsive Behavior / Q000208:ethnology / Q000235:genetics*; D007266:Inhibition, Psychological; D015810:Linkage Disequilibrium; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011493:Protein Kinase C / Q000235:genetics*; D019966:Substance-Related Disorders / Q000208:ethnology / Q000235:genetics; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: C087857:protein kinase C gamma; D011493:Protein Kinase C