Abstract: Objective To investigate the interactive effect of genetic and environmental factors on the susceptibility to stress response among white-collar workers.Methods With stratified cluster sampling,we recruited 323 persons with scores of Job Stress Survey(JSS) higher than 90% of the normal reference value derived from a screening survey on occupational stress with JSS among 3200 Han white-collar workers.All the participants were surveyed with Life Event Scale(LES) and Social Support Rating Scale,and their blood samples were collected and genotyped for 4 locus of glucocorticoid receptor gene(GCCR:Rs10482605,Rs41423247,Rs258747,Rs17209237) with Snapshot technology.Results The participants with the mutation type of GCCR rs10482605 had a significantly higher average JSS score than those with the wild type(3.34±0.09 vs.3.28±0.07,P<0.05);the participants with the mutation type of GCCR rs17209237 had a significantly higher overall LES score than those with the wild type(49.41±15.60 vs.45.76±15.77,P<0.05).The mutated GCCR rs41423247 presented a negative multiplicative interaction to subjective social support(odds ratio=0.237,P<0.05).Conclusion Gene GCCR may be a genetic risk factor for stress response and may have interactive effect with environmental factors on stress response in human.