Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim, J5, 68159 Mannheim, Germany.
Psychoneuroendocrinology. 2011 Aug;36(7):1010-20. doi: 10.1016/j.psyneuen.2010.12.015. Epub 2011 Jan 26.
Interindividual variability in the regulation of the human stress system accounts for a part of the individual's liability to stress-related diseases. These differences are influenced by environmental and genetic factors. Early childhood adversity is a well-studied environmental factor affecting an individual's stress response which has been shown to be modulated by gene-environment interaction (GxE). Neuropeptide Y (NPY) plays a role in stress regulation and genetic variation in NPY may influence stress responses. In this study, we analyzed the association of a common variant in the NPY gene promoter, rs16147, with cortisol and ACTH responses to acute psychosocial stress in young adults from the Mannheim Study of Children at Risk (MARS), an ongoing epidemiological cohort study following the outcome of early adversity from birth into adulthood. We found evidence of a GxE interaction between rs16147 and early adversity significantly affecting HPA axis responses to acute psychosocial stress. These findings suggest that the neurobiological mechanisms linking early adverse experience and later neuroendocrine stress regulation are modulated by a gene variant whose functional relevance is documented by increasing convergent evidence from in vitro, animal and human studies.
个体间人类应激系统调节的变异性解释了个体对应激相关疾病易感性的一部分原因。这些差异受环境和遗传因素的影响。童年逆境是一个研究充分的环境因素，它影响个体的应激反应，并且已经证明其受到基因-环境相互作用（GxE）的调节。神经肽 Y（NPY）在应激调节中发挥作用，NPY 的遗传变异可能影响应激反应。在这项研究中，我们分析了 NPY 基因启动子中的常见变异 rs16147 与皮质醇和 ACTH 对来自曼海姆风险儿童研究（MARS）的年轻人急性心理社会应激反应的关联，MARS 是一项正在进行的队列研究，从出生开始一直到成年，追踪早期逆境的结果。我们发现 rs16147 与早期逆境之间存在 GxE 相互作用，这显著影响了 HPA 轴对急性心理社会应激的反应。这些发现表明，将早期不良经历与后期神经内分泌应激调节联系起来的神经生物学机制受到基因变异的调节，而越来越多的来自体外、动物和人类研究的证据证明了该基因变异的功能相关性。
