FKBP5 and CRHR1 polymorphisms moderate the stress-physical health association in a national sample.

OBJECTIVE: Stressful life events experienced during childhood and as an adult negatively impact mental and physical health over the life span. This study examined polymorphisms from 2 hypothalamic-pituitary-adrenal axis-related genes previously associated with posttraumatic stress disorder-FKBP5 and CRHR1-as moderators of the impact of child abuse and adult stress on physical health. METHOD: A national, community-based subsample of non-Hispanic European American respondents (n = 527) from a prospective longitudinal 3-year study of stress and coping (N = 2,729) provided saliva for genotyping. RESULTS: FKBP5 (rs1360780) and CRHR1 (rs12944712) polymorphisms significantly interacted with child abuse and adult stress to predict increases in physical health ailments over 3 years. Child abuse and adult stress were strongly related to physician-diagnosed physical ailments among individuals with the risk alleles of both single nucleotide polymorphisms. Individuals carrying the low-risk homozygotic genotypes were protected from the long-term negative health implications of experiencing both child abuse and adult stress. CONCLUSION: Consistent with theories linking the hypothalamic-pituitary-adrenal axis with stress-related disease, hypothalamic-pituitary-adrenal axis polymorphism genotypes moderated the association between exposure to child abuse/adult stress and long-term physical health outcomes in a national sample.