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

Abstract

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.