Associations of GR and ACTHR gene polymorphisms with quantitative trait of strain

Abstract

To explore association between GR and ACTHR gene polymorphisms and quantitative trait of stress in Chinese Han population. Four polymorphic markers (GRA5556G, A5556G, GAGG4534/4536AAAG, promoter T-2C) in GR gene and ACTHR gene were genotyped with PCR-RLFP in 200 healthy Hans. ISTA6.0 and life event stressor questionnaire was used to assess stressors. JSS, SCL-90 and GWB questionnaires were used to quantify the phenotypes of stress. Blood cortical and ACTH levels, and nervous behavior function were measured to assess Physiological strain. CWAI questionnaire was used to assess work ability. Then strain was assessed with Structural equation modeling (SEM). The subjects with GR A5556G genotype (G/A) showed significantly higher plasma cortisol levels, higher psychological stress scores, lower work ability scores and lower plasma ACTH levels compared with the subjects with wild-type (P < 0.01). Psychological stress scores and plasma cortisol levels in the subjects with GR GAGG4534/4536AAAG AG genotype were significantly higher than those in the subjects with wild-type, but the reaction and action sensitivity in the subjects with GR GAGG4534/4536AAAG AG genotype were significantly lower than those in ones with wild-type (P < 0.01). The ACTH level in the subjects with ACTHR promoter T-2C T/T genotype was significantly lower than that in ones with C/C and C/T genotype (P < 0.01). Interaction of GRA5556G and GG4534/4536AAAG with plasma cortisol was positively associated (βs = 0.543, P < 0.01), but with SCL-90 score was negatively associated (βs = -0.374, P < 0.01). Interaction of GRA5556G and GGC6294G with plasma cortisol was correlated (βs = 0.465, P < 0.05). While GR and ACTHR gene variants are the risk factors for psychological strain, physiological strain and decreased work ability (βs are 0.62, 0.43, -0.74, respectively (P < 0.01). While scarce social support, job stressors, negative life stressors and dangerous individual characters are the risk factors for occupational strain, psychological strain, physiological strain and decreased work ability (P < 0.01). GRA5556G, GRA5556G, GAGG4534/4536AAAG and ACTHR promoter T-2C variants might be associated with quantitative trait of strain, and GR and ACTHR gene variants with stressors increased the risk for developing strain.