Abstract
The adenylate cyclase activating polypeptide 1 (pituitary) receptor (ADCYAP1R1) gene is associated with the hypothalamic-pituitary-adrenal (HPA) axis, which controls stress responses. The single-nucleotide polymorphism of ADCYAP1R1, rs2267735, has been investigated in many studies to test its association with posttraumatic stress disorder (PTSD), but the results have not been consistent. It is worth systematically exploring the role of rs2267735 in PTSD development. In this study, we analyzed rs2267735 in 1,132 trauma-exposed Chinese individuals (772 females and 360 males). We utilized the PTSD checklist for DSM-5 (PCL-5) to measure the PTSD symptoms. Then, we analyzed the main, G × E (rs2267735 × trauma exposure), and G × G (with other HPA axis gene polymorphisms) effects of rs2267735 on PTSD severity (total symptoms). There were no significant main or G × E effects (P > 0.05). The G × G ADCYAP1R1-FKBP5 interaction (rs2267735 × rs1360780) was associated with PTSD severity (beta = −1.31 and P = 0.049) based on all subjects, and the G × G ADCYAP1R1-CRHR1 interaction (rs2267735 × rs242924) was correlated with PTSD severity in men (beta = −4.72 and P = 0.023). Our study indicated that the ADCYAP1R1 polymorphism rs2267735 may affect PTSD development through diverse gene-gene interactions.
Highlights
ADCYAP1R1, an HPA Axis Gene, Is Associated With Stress ResponseThe pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor (PAC1) are widely distributed in hypothalamic and limbic structures [1,2,3,4,5,6]
Our findings suggested that ADCYAP1R1 might affect PTSD in men in a specific manner by interacting with CRHR1
We have provided additional genetic findings regarding the HPA axis and its involvement in PTSD and indicated that the ADCYAP1R1 polymorphism rs2267735 may affect PTSD development through diverse gene–gene interactions
Summary
The pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor (PAC1) are widely distributed in hypothalamic and limbic structures [1,2,3,4,5,6]. This peptide and receptor help regulate responses to anxiety-provoking stimuli or stress [3, 7,8,9,10]. The ADCYAP1R1 gene, which encodes the receptor PAC1, is associated with the neuroendocrine system hypothalamic–pituitary–adrenal (HPA) axis that is involved in controlling mammalian stress responses [11, 12]. Rs2267735 could regulate the normal stress response by affecting the bind of estrogen receptors alpha and estrogen response element [16]
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