Social regulation of gene expression in human leukocytes.

TitleSocial regulation of gene expression in human leukocytes.
Publication TypeJournal Article
Year of Publication2007
AuthorsCole SW, Hawkley LC, Arevalo JM, Sung CY, Rose RM, Cacioppo JT
JournalGenome Biol
Date Published2007
KeywordsAged, C-Reactive Protein, Computational Biology, Female, Gene Expression Regulation, Genome, Human, Glucocorticoids, Humans, Interpersonal Relations, Leukocytes, Male, Middle Aged, Models, Biological, Promoter Regions, Genetic, Signal Transduction

BACKGROUND: Social environmental influences on human health are well established in the epidemiology literature, but their functional genomic mechanisms are unclear. The present study analyzed genome-wide transcriptional activity in people who chronically experienced high versus low levels of subjective social isolation (loneliness) to assess alterations in the activity of transcription control pathways that might contribute to increased adverse health outcomes in social isolates.

RESULTS: DNA microarray analysis identified 209 genes that were differentially expressed in circulating leukocytes from 14 high- versus low-lonely individuals, including up-regulation of genes involved in immune activation, transcription control, and cell proliferation, and down-regulation of genes supporting mature B lymphocyte function and type I interferon response. Promoter-based bioinformatic analyses showed under-expression of genes bearing anti-inflammatory glucocorticoid response elements (GREs; p = 0.032) and over-expression of genes bearing response elements for pro-inflammatory NF-kappaB/Rel transcription factors (p = 0.011). This reciprocal shift in pro- and anti-inflammatory signaling was not attributable to differences in circulating cortisol levels, or to other demographic, psychological, or medical characteristics. Additional transcription control pathways showing differential activity in bioinformatic analyses included the CREB/ATF, JAK/STAT, IRF1, C/EBP, Oct, and GATA pathways.

CONCLUSION: These data provide the first indication that human genome-wide transcriptional activity is altered in association with a social epidemiological risk factor. Impaired transcription of glucocorticoid response genes and increased activity of pro-inflammatory transcription control pathways provide a functional genomic explanation for elevated risk of inflammatory disease in individuals who experience chronically high levels of subjective social isolation.

Alternate JournalGenome Biol.
PubMed ID17854483
PubMed Central IDPMC2375027
Grant ListP01 AG19811 / AG / NIA NIH HHS / United States
P20 RR020645 / RR / NCRR NIH HHS / United States
R01 AI52737 / AI / NIAID NIH HHS / United States
R01 CA116778 / CA / NCI NIH HHS / United States