Whole blood gene expression and interleukin-6 levels

• We studied the association of gene expression with interleukin-6 levels in participants from Framingham Heart Study
• The results were in 694 participants from InCHIANTI study
• We identified and replicated 807 genes that were associated with circulating interleukin-6 levels
• Many of the interleukin-6 associated genes are involved in inflammation-related pathways or erythrocyte function

BackgroundCirculating interleukin-6 levels increase with advancing age and are a risk factor for various diseases and mortality. The characterization of gene expression profiles associated with interleukin-6 levels might suggest important molecular events underlying its regulation.Methods and resultsWe studied the association of transcriptional profiles with interleukin-6 levels in 2422 participants from the Framingham Heart Study Offspring Cohort using Affymetrix Human Exon 1.0 ST Array. We identified 4139 genes that were significantly associated with interleukin-6 levels (FDR < 0.05) after adjusting for age, sex and blood cell components. We then replicated 807 genes in the InCHIANTI study with 694 participants. Many of the top genes are involved in inflammation-related pathways or erythrocyte function, including JAK/Stat signaling pathway and interleukin-10 signaling pathway.ConclusionWe identified and replicated 807 genes that were associated with circulating interleukin-6 levels. Future characterization of interleukin-6 regulation networks may facilitate the identification of additional potential targets for treating inflammation-related diseases.