Salivary Biomarkers (DNA, RNA and Cortisol), Life Stress and Nicotine Dependence

唾液生物标志物（DNA、RNA 和皮质醇）、生活压力和尼古丁依赖

• 批准号: 7941751
• 负责人: Judy A Andrews
• 金额: $ 88.63万
• 依托单位: OREGON RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7941751
• 关键词: Address; Adolescence; Age; Alcohol or Other Drugs use; Anxiety Disorders; Area; Arts; Biological Markers; Candidate Disease Gene; Caring; Catechol O-Methyltransferase; Childhood; Chronic; Chronic stress; Clinical; Clinical assessments; Collection; Corticotropin-Releasing Hormone Receptors; DNA; DRD2 gene; Data; Depressive disorder; Development; Diagnostic; Disease; Environment; Etiology; Event; Exposure to; Failure; Foundations; Gene Expression; Gene Expression Profile; Genes; Genetic; Genetic Polymorphism; Goals; Hydrocortisone; Individual; Intervention; Intervention Studies; Interview; Laboratories; Life; Life Stress; Link; Longitudinal Studies; Lymphocyte; Measurement; Measures; Methyltransferase Gene; Moods; National Institute of Drug Abuse; Nicotine; Nicotine Dependence; Noise; Opioid Receptor; Parents; Participant; Pathway interactions; Preventive Intervention; Promoter Regions; Protein Kinase; Questionnaires; RNA; Receptor Gene; Recovery; Research; Research Infrastructure; Research Project Grants; Respondent; Rewards; Saliva; Salivary; Sampling; Schedule; Signal Transduction; Source; Specific qualifier value; Stress; Structure; Substance Use Disorder; Tobacco use; Translational Research; Trier Social Stress Test; United States National Institutes of Health; Validation; Youth; base; cohort; drug abuse prevention; emerging adult; emerging adulthood; experience; functional genomics; genome-wide; improved; novel; prevent; public health relevance; response; serotonin transporter; stressor; success; therapy design; tool

DESCRIPTION (provided by applicant): The broad goal of this project is to lay the foundation for research identifying salivary biomarkers that are predictive of the vulnerability of individuals to (a) progress toward nicotine dependence and (b) ultimately to become dependent on nicotine by emerging adulthood, given their exposure to life stress. Features of the proposed research is the use of an interview-based life stress assessment to provide a precise and reliable measurement of chronic and episodic stress, and initial steps in the identification of easily obtained salivary biomarkers that identify individuals who are exposed to greater levels of chronic stress. This project has the potential to advance drug abuse prevention and intervention research through identifying Genetic x Environment (GxE) interactions, which may help to explain the success or failure of interventions designed to prevent the initiation of tobacco use and the progression to nicotine dependence, or to maintain cessation. The proposed assessment with two cohorts at age 20/21 (n = 390) includes saliva collection for DNA extraction to assess polymorphisms of candidate genes known to be related to the stress-reward pathway, saliva collection for RNA extraction for candidate gene and genome wide gene expression, and a systematic contextual based assessment of chronic and episodic stress, using state-of-the-art assessment tools, at age 20/21. The data from this assessment will be integrated with other multi-source/multi-respondent data from two cohorts from an ongoing eleven-year longitudinal study examining the etiology of substance use, including nicotine dependence, combined with data assessing cortisol reactivity in response to laboratory induced stress, at age 20/21. To accomplish this broad goal, we propose to address the following aims: (1) Identify GxE interactions which predict change in nicotine dependence across from adolescence to emerging adulthood and across youth from the occurrence of polymorphisms of specified candidate gene known to be related to the stress reward pathway in the context of the experience of chronic and episodic stress; (2) Assess the association between specific genetic polymorphisms and cortisol reactivity in response to a laboratory induced stressor and assess the effect of GxE interactions on cortisol dysregulation through examining the effect of the interaction of genetic polymorphisms and life stress in emerging adulthood on cortisol dysregulation; and (3) Evaluate whether the salivary transcriptome contains RNA biomarkers for the identification of individuals with the gene expression signature of chronic stress using RNA samples from 24 individuals who experience the most life stress and 24 individuals with the least stress. We plan to validate an existing functional genomic signature of chronic stress previously identified in lymphocytes by performing gene expression analysis of individual candidate genes, and we will discover, confirm and validate novel candidate genes by performing genome-wide and candidate gene expression analysis. PUBLIC HEALTH RELEVANCE: This project has the potential to advance drug abuse prevention and intervention research through identifying Genetic x Environment (GxE) interactions, which may help to explain the success or failure of interventions designed to prevent the initiation of tobacco use and the progression to nicotine dependence, or to maintain cessation. Results may guide the selection of tailored interventions for specific individuals.

描述（由申请人提供）：该项目的广泛目标是为识别唾液生物标志物的研究奠定基础，这些唾液生物标志物可以预测个人对（a）朝着尼古丁依赖性的脆弱性以及（b）最终通过出现的成年后的成年后依赖尼古丁的脆弱性，鉴于他们对生活压力的影响。拟议的研究的特征是使用基于访谈的生活压力评估来提供对慢性和情节压力的精确和可靠的测量，以及鉴定易于获得的唾液生物标志物的初步步骤，这些唾液生物标志物识别出暴露于慢性压力水平的人。该项目有可能通过识别遗传X环境（GXE）相互作用来推动预防药物滥用和干预研究，这可能有助于解释旨在防止烟草使用的干预措施的成功或失败，并进步到尼古丁依赖性或维持戒烟。 The proposed assessment with two cohorts at age 20/21 (n = 390) includes saliva collection for DNA extraction to assess polymorphisms of candidate genes known to be related to the stress-reward pathway, saliva collection for RNA extraction for candidate gene and genome wide gene expression, and a systematic contextual based assessment of chronic and episodic stress, using state-of-the-art assessment tools, at age 20/21.来自该评估的数据将与来自持续的11年纵向研究的其他多源/多响应数据集成，研究了包括尼古丁依赖性（包括尼古丁依赖性）的病因，并结合了20/21岁的实验室诱导压力的响应对实验室诱导的压力的皮质醇反应性的数据。为了实现这一广泛目标，我们建议解决以下目的：（1）确定GXE相互作用，这些相互作用可预测从青春期到新兴成年期以及年轻人的尼古丁依赖性变化，以及在慢性和情节压力的经历中与压力奖励途径相关的特定候选基因的多态性的发生因素而发生的。 （2）评估特定遗传多态性与皮质醇反应性响应实验室诱导的压力源之间的关联，并通过检查遗传多态性和生命应激的相互作用在出现的掺杂对皮质醇失调中的遗传多态性和生命应激的相互作用，以评估GXE相互作用对皮质醇失调的影响； （3）评估唾液转录组是否含有RNA生物标志物，用于使用来自24个经历最大生命压力的人和24个人的24个个体的RNA样本来鉴定具有慢性应激基因表达特征的个体。我们计划通过对单个候选基因进行基因表达分析来验证先前在淋巴细胞中鉴定出的慢性应激的现有功能基因组特征，我们将通过进行全基因组和候选基因表达分析来发现，确认和验证新型候选基因。公共卫生相关性：该项目有可能通过识别遗传X环境（GXE）相互作用来推动预防药物滥用和干预研究，这可能有助于解释旨在防止烟草使用以及对尼古丁依赖性的进展或维持us缩的干预措施的成功或失败。结果可以指导针对特定个体的量身定制干预措施的选择。