Social regulation of gene expression in human leukocytes

Steve W Cole¹^,2^,3 , Louise C Hawkley⁴ , Jesusa M Arevalo¹ , Caroline Y Sung² , Robert M Rose⁵ and John T Cacioppo⁴

¹Department of Medicine, Division of Hematology-Oncology, UCLA School of Medicine, Los Angeles CA 90095-1678, USA

²UCLA AIDS Institute, UCLA Molecular Biology Institute, Jonsson Comprehensive Cancer Center

³Norman Cousins Center

⁴Department of Psychology, and Center for Cognitive and Social Neuroscience, University of Chicago

⁵Institute for Medical Humanities, University of Texas Medical Branch at Galveston, and the John D and Catherine T MacArthur Foundation

author email corresponding author email

Genome Biology 2007, 8:R189doi:10.1186/gb-2007-8-9-r189


Published:	13 September 2007

Subject areas: Neurobiology, Immunology, Genome studies

Abstract

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-κB/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.