Association Between BclI SNP of the Glucocorticoid Receptor (GCR) And Immune Response to Stress

Stress influences immunity through various mechanisms including immunoregulatory elements. Previous studies show associations between high stress levels and altered immune balance such as in TH1/TH2 (IFNγ, IL‐4, IL‐10) cytokine production. Such immunoregulatory imbalances are associated with altered serum cortisol levels and can be reproduced with glucocorticoids (GC) in vitro . GC act through the GCR for which several SNPs have been described. The GCR SNPs BclI and N363S are associated with hyperreactivity to GC. We examined the associations between GCR SNPs and cytokine responses. 86 normal volunteers were stratified into four groups by k‐means clustering using Perceived Stress Score (PSS) and immunologic variables. We examined numbers of CD4+CD25+FoxP3+ (T reg ) and CD4+ cells producing TH1/TH2 cytokines by intracellular flow cytometry. DNA was extracted from peripheral blood and SNP determined by PCR and RFLP analysis. Clusters were categorized by PSS into high stress (HS‐19.2±3.5, n=15), low stress (LS‐8.3±4.7, n=7) and two groups of typical stress (TS‐12.6±5.0, n=37 and 12.7±6.3, n=27). The HS cluster had decreased T reg (2.0±0.6%) and TH1 (22.1±4.4%) compared to the LS cluster with higher T reg (3.5±1.1%) and TH1 (33.4±6.7). There were no cluster differences in IL‐4 and IL‐10. BclI (but not N363S) SNP showed a trend in C/C homozygosity in 66.7% (10/15) of the HS compared to 28.6% (2/7) of the the LS cluster (χ 2 (1)=2.79, p=0.095). These results suggest that genetic variation, such as GCR BclI SNP, may participate in regulation of immune response to stress.