The −2T/C polymorphism in the adrenocorticotropin receptor gene affects stress perception of patients with alopecia areata


  • Conflicts of interest: None.


Fei Hao, phd

Department of Dermatology

The Third Military Medical University

Chongqing 400038





Altered hypothalamic–pituitary–adrenal (HPA) axis response involved in the pathogenesis of stress-associated alopecia areata (AA) has been reported. A novel polymorphism −2T>C of the adrenocorticotropin receptor (ACTHR) can result in an insufficient HPA response to stress; therefore, the functional polymorphism may underlie a role in stress-associated AA.


To investigate the relationship between psychosocial factors and the risk of developing AA and to detect the association between the −2T>C polymorphism of ACTHR and AA.


Stressful situations were evaluated using Holmes and Rahe's social readjustment rating scale. The ACTHR −2T>C polymorphism was examined in 263 patients with AA and 241 controls.


Significant elevation of psychological stress experienced by some patients with AA compared with controls (Z = 6.628, P < 0.01). The frequency of the ACTHR C allele showed a significant difference between patients with AA and controls (P = 0.004). Allele C is the risk allele with a dominant model as the −2C allele occurred more often in patients with AA (P = 0.001). There were significant differences between patients with AA with a severe stress attack versus patients with AA with no obvious stress (P < 0.001), whereas the genotype frequencies were not correlated with the type, duration of disease, and age at onset. Notably, the C allele carrier was significantly associated with stress risk in both AA and controls (P = 0.002, OR = 1.576, 95% CI: 1.148–2.162; P = 0.042, OR = 1.529, 95% CI: 1.022–2.288).


These findings suggest AA in some patients may be associated with stress. The ACTHR gene −2T>C variant may be one important factor that influences stress perception of patients with AA.