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| Status |
Public on Feb 01, 2012 |
| Title |
Inter-ethnic differences in lymphocyte sensitivity to glucocorticoids reflect variation in transcriptional response |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Glucocorticoids (GCs) are steroid hormones widely used as pharmaceutical interventions, which act mainly by regulating gene expression levels. A large fraction of patients (~30%), especially those of African descent, show a weak response to treatment. To interrogate the contribution of variable transcriptional response to inter-ethnic differences, we measured in vitro lymphocyte GC sensitivity (LGS) and transcriptome-wide response to GCs in peripheral blood mononuclear cells (PBMCs) from African-American and European-American healthy donors. We found that transcriptional response after 8hrs treatment was significantly correlated with variation in LGS within and between populations. We found that NFKB1, a gene previously found to predict LGS within populations, was more strongly downregulated in European-Americans on average. NFKB1 could not completely explain population differences, however, and we found an additional 177 genes with population differences in the average log2 fold change (FDR<0.05), most of which also showed a weaker transcriptional response in AfricanAmericans. These results suggest that inter-ethnic differences in GC sensitivity reflect variation in transcriptional response at many genes, including regulators with large effects (e.g. NFKB1) and numerous other genes with smaller effects.
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| Overall design |
Total RNA was obtained from paired aliquots of peripheral blood mononuclear cells treated with dexamethasone or vehicle (EtOH) for 8 and 24 hours.
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| Contributor(s) |
Maranville JC, Baxter SS, Torres JM, Di Rienzo A |
| Citation(s) |
22158329 |
| Submission date |
Nov 12, 2011 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Joseph C Maranville |
| E-mail(s) |
jcmaranville@uchicago.edu
|
| Phone |
7738345239
|
| Organization name |
920 E. 58th Street
|
| Street address |
920 E. 58th Street
|
| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60637 |
| Country |
USA |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (48)
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| Relations |
| BioProject |
PRJNA148657 |
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