To determine whether the increased transcription of immune activation genes in social isolates might stem from reductions in GR-mediated transcriptional activity (despite broadly similar levels of its cortisol ligand), we performed Transcription Element Listening System (TELiS) bioinformatics analysis of promoter DNA sequences [41]. Analyses of glucocorticoid response element (GRE) prevalence in differentially expressing promoters indicated significant under-expression of GR target genes in leukocytes from socially isolated individuals. The prevalence of TRANSFAC V$GR_Q6 transcription factor-binding motifs (TFBMs) was 63% lower in regulatory sequences of genes over-expressed in high-lonely individuals versus genes over-expressed in low-lonely individuals (mean = 0.257 ± 0.063 versus 0.094 ± 0.041; p = 0.0325). Similar results emerged in sensitivity analyses that parametrically varied the length of promoter sequence scanned (-300 bp, -600 bp, -1,000 to +200 bp from transcription start site) and the stringency of promoter sequence match to the TFBM consensus motif (MatSim score = 0.80, 0.90, 0.95), with an average 0.53-fold (± 0.10) difference across all 9 parametric combinations (p = 0.0020). Similar results also emerged from sensitivity analyses utilizing a more stringent definition of differential
