GENETIC STUDY: 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.

Genetic variations in the PRKCG gene and osteosarcoma risk in a Chinese population: a case-control study

“…The result is consistent with the conventionally view that variants in the functional region can effect expression of γPKC normally. For example, the study by Schlaepfer et al discovered that rs3745406 polymorphisms of PRKCG was a susceptibility locus for human disease in samples of Caucasian, which also supports the relationship between gene variation and neuropathic disease [16]. Meanwhile, our results demonstrated that γPKC, which encodes by PRKCG gene, played an important role in the central nervous system's transmembrane signal transduction, and the results was accordant with the previous studies [24].…”

“…1 Linkage disequilibrium of the 12 tag SNPs in PRKCG gene as a complex process and was not clear, but it was universally acknowledged that environment carcinogens could induce genomic polymorphism, such as oxidative stress, drinking, smoking, and ionizing radiation [9,10]. Previous research found that genetic variants of PRKCG can initiate the onset of homologous diseases, such as behavioral disinhibition, major depressive disorder, and myotonic dystrophy [16,17,24]. Therefore, in the present study, we aimed to study the involvement between five SNPs of PRKCG (rs2547362, rs3745406, rs454006, rs8103851, rs2242245) and risk of osteosarcoma in the ethnically Han Chinese.…”

“…Schlaepfer et al found that rs2242244 and rs307941 variants of PRKCG gene could elevate susceptibility of behavioral disinhibition [16]. Missense variants in exon 4 (C114Y/G123R/G123E) of PRKCG gene has the relationship with spinocerebellar ataxia type 14 [4,17,18].…”

The CHRNA5/A3/B4 Gene Cluster Variability as an Important Determinant of Early Alcohol and Tobacco Initiation in Young Adults

“…The pool of potential subjects encompassed over 5000 youth; we selected for inclusion in this study those assessed between ages 17 and 21 (mean age 18 ± 1.50). A more detailed description of this sample has been published elsewhere (22). A description of the study was presented to all subjects, who signed written informed assent (minors) or consent (adults) to participate.…”

Inferring Causation from Cross-Sectional Data: Examination of the Causal Relationship between Hyperactivity–Impulsivity and Novelty Seeking

“…In ADHD, where arousal regulation may be dysfunctional (van der Meere, 2002; O'Connell et al, 2008), this may result in a complex interplay between novelty seeking and hyperactive behaviors in attempting to regulate or optimize arousal levels. However, apart from evidence that both phenotypes contribute to a highly heritable latent trait (Young et al, 2000; Schlaepfer et al, 2007), to our knowledge, studies have yet to address the etiological links between childhood hyperactive–impulsive symptoms and novelty seeking scores in quantitative genetic studies.…”