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

Background Altered hypothalamic–pituitary–adrenal ( HPA ) axis response involved in the pathogenesis of stress‐associated alopecia areata ( AA ) has been reported. A novel polymorphism −2 T > 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 . Objective To investigate the relationship between psychosocial factors and the risk of developing AA and to detect the association between the −2 T > C polymorphism of ACTHR and AA . Methods Stressful situations were evaluated using H olmes and R ahe's social readjustment rating scale. The ACTHR −2 T > C polymorphism was examined in 263 patients with AA and 241 controls. Results 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 −2 C 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). Conclusions These findings suggest AA in some patients may be associated with stress. The ACTHR gene −2 T > C variant may be one important factor that influences stress perception of patients with AA .