The human protein kinase C gamma gene (PRKCG) as a susceptibility locus for behavioral disinhibition

Addict Biol. 2007 Jun;12(2):200-9. doi: 10.1111/j.1369-1600.2007.00063.x.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antisocial Personality Disorder / ethnology
  • Antisocial Personality Disorder / genetics
  • Attention Deficit Disorder with Hyperactivity / ethnology
  • Attention Deficit Disorder with Hyperactivity / genetics
  • Blacks / genetics
  • Chromosome Mapping
  • Conduct Disorder / ethnology
  • Conduct Disorder / genetics*
  • Exploratory Behavior
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Haplotypes
  • Hispanic or Latino / genetics
  • Humans
  • Impulsive Behavior / ethnology
  • Impulsive Behavior / genetics*
  • Inhibition, Psychological*
  • Linkage Disequilibrium
  • Male
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics*
  • Protein Kinase C / genetics*
  • Substance-Related Disorders / ethnology
  • Substance-Related Disorders / genetics
  • Whites / genetics

Substances

  • protein kinase C gamma
  • Protein Kinase C