A Single Nucleotide Polymorphism of the Neuropeptide B/W Receptor-1 Gene Influences the Evaluation of Facial Expressions

Abstract

Neuropeptide B/W receptor-1 (NPBWR1) is expressed in discrete brain regions in rodents and humans, with particularly strong expression in the limbic system, including the central nucleus of the amygdala. Recently, Nagata-Kuroiwa et al. reported that Npbwr1 −/− mice showed changes in social behavior, suggesting that NPBWR1 plays important roles in the emotional responses of social interactions.The human NPBWR1 gene has a single nucleotide polymorphism at nucleotide 404 (404A>T; SNP rs33977775). This polymorphism results in an amino acid change, Y135F. The results of an in vitro experiment demonstrated that this change alters receptor function. We investigated the effect of this variation on emotional responses to stimuli of showing human faces with four categories of emotional expressions (anger, fear, happiness, and neutral). Subjects' emotional levels on seeing these faces were rated on scales of hedonic valence, emotional arousal, and dominance (V-A-D). A significant genotype difference was observed in valence evaluation; the 404AT group perceived facial expressions more pleasantly than did the 404AA group, regardless of the category of facial expression. Statistical analysis of each combination of [V-A-D and facial expression] also showed that the 404AT group tended to feel less submissive to an angry face than did the 404AA group. Thus, a single nucleotide polymorphism of NPBWR1 seems to affect human behavior in a social context.

Transient expression of neuropeptide W in postnatal mouse hypothalamus – A putative regulator of energy homeostasis

“…The physiological function of NPBWR1 has been characterized by the phenotypical analysis of NPBWR1 null mice, which showed late onset obesity (Ishii et al, 2003), abnormal social interaction, and an aberrant autonomic response to physical stress (Nagata-Kuroiwa et al, 2011). A single nucleotide polymorphism of the human NPBWR1 gene has been shown to influence the ability to evaluate facial expressions (Watanabe et al, 2012). In contrast, the physiological function of NPBWR2 in primates has not been elucidated.…”

Mesolimbic neuropeptide W coordinates stress responses under novel environments

“…These mice also show abnormal social interaction and an aberrant autonomic response to physical stress (21). Recently, an SNP of the human NPBWR1 gene has been shown to influence the evaluation of facial expressions (22). We and other groups have isolated neuropeptide B (NPB) and neuropeptide W (NPW) as cognate endogenous ligands for NPBWR1 and NPBWR2 (23)(24)(25)(26).…”

NPBWR1 and NPBWR2: Implications in Energy Homeostasis, Pain, and Emotion

“…Recent studies in Npbwr1 −/− mice support this concept (Table 2). Furthermore, a recent report suggested that a human polymorphism in the NPBWR1 gene might affect emotional responses to facial expressions (Watanabe et al, 2012). In daily life, people show various emotional reactions to others depending on their personalities, even in the same situation.…”

“…Importantly, this polymorphism causes an amino acid substitution (Y135F) within the highly conserved DRY motif of G-protein-coupled receptors at the junction of the third transmembrane domain and second intracellular loop, which is known to play an important role in G-protein coupling. Recently, Watanabe et al (2012) demonstrated that this change partially impairs receptor function as measured by inhibition of cAMP production. Furthermore, this variation affects the emotional response to stimuli showing human faces with four categories of emotional expression (anger, fear, happiness, and neutral).…”