Very limited information is known about the neurobiological relevance of mutations of the PENK gene. Thus, given that the current PENK SNPs studied are within noncoding regions of the gene, we examined their potential relationship to PENK mRNA expression levels in the postmortem striatum and amygdala, regions highly implicated in emotional regulation in normal human subjects. PENK mRNA is expressed throughout the striatum and predominantly in the central nucleus of the amygdaloid complex ( Figure 4 ). A strong significant association was detected between the PENK SNPs and mRNA expression in the central amygdala (rs2576573 F1,15 = 13.43, p = 0.003). Overall, control subjects with the A allele of the rs2576573 SNPs had higher PENK expression ( Figure 4 ). In the striatum, PENK mRNA expression was significantly influenced by age and only a trend-genotype effect was detected in the nucleus accumbens core (F1,10 = 3.778, p = 0.084). A gene-dose effect was also evident for the rs2609997 SNP in the central amygdala (F2,15 = 5.577, p = 0.018) with C/C subjects having higher PENK mRNA expression, but there were few homozygous subjects, so this SNP could not be fully evaluated in the postmortem population.
