Experienced discrimination and racial differences in leukocyte gene expression.

Area of Science:

• Molecular biology
• Health disparities research
• Bioinformatics

Background:

• Racial disparities in health outcomes are well-documented but not fully understood.
• Chronic inflammation and stress exposure, like racial discrimination, are implicated in diseases with racial disparities, such as HIV.
• The conserved transcriptional response to adversity (CTRA) links stress to pro-inflammatory processes.

Purpose of the Study:

• To investigate the relationship between perceived ethnic discrimination and the activity of pro-inflammatory, neuroendocrine, and antiviral pathways in leukocytes.
• To examine the independent effects of race and HIV status on CTRA pathways.
• To explore the modifying role of perceived discrimination on these pathways.

Main Methods:

• Cross-sectional bioinformatic analyses.
• Measurement of perceived discrimination using the Perceived Ethnic Discrimination Questionnaire (PED-Q).
• Analysis of transcription factor pathway activity in peripheral blood leukocytes from 71 African American/Black and European American/White participants (HIV+ and HIV-).

Main Results:

• African Americans exhibited higher activity in pro-inflammatory (NF-κB, AP-1) and stress-responsive (CREB, glucocorticoid receptor) pathways compared to European Americans.
• These racial differences in pathway activity were not significantly modified by HIV infection.
• Perceived racial discrimination potentially explained over 50% of the race-related difference in pro-inflammatory transcription factor activity.

Conclusions:

• Differential exposure to racial discrimination may drive racial disparities in health outcomes.
• Activation of threat-related molecular programs, including inflammation, by discrimination contributes to chronic illness risk.
• Understanding these molecular mechanisms is crucial for addressing health inequities.