Evaluation of genetic and metabolic markers in the development of urinary urgency incontinence

尿急性尿失禁发生过程中遗传和代谢标志物的评估

• 批准号: 10591708
• 负责人: DAVID SHEYN
• 金额: $ 9.81万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10591708
• 关键词: Acetylcholine; Affect; Aging; Anxiety; Bladder; Bladder Control; Brain; Cardiovascular Diseases; Central Nervous System; Characteristics; Choline; Choline O-Acetyltransferase; Classification; Clinical; Coenzymes; Data; Development; Diagnosis; Diet; Dietary intake; Disease; Early Intervention; Enzymes; Esthesia; Etiology; Evaluation; Fishes; Food; Functional disorder; Genetic; Genetic Markers; Incidence; Incontinence; Intake; Intervention; Kidney Diseases; Knowledge; Lead; Lecithin; Link; Measures; Meat; Mental Depression; Metabolic; Metabolic Marker; Metabolism; Methods; Mus; Nervous System; Neurologic; Neurons; Neurotransmitters; Nurses' Health Study; Nutrient; Onset of illness; Organ; Pathway interactions; Patients; Pelvic floor structure; Peripheral; Persons; Phenotype; Phosphorylcholine; Plasma; Prevalence; Prevention strategy; Process; Prospective cohort; Psychological Stress; Public Health; Quality of life; Reporting; Research; Risk; Risk Factors; Serum; Severities; Signal Transduction; Single Nucleotide Polymorphism; Sphingomyelins; System; United States; Urinary Incontinence; Woman; Women' s Health; age related; body system; choline deficient diet; cholinergic; comparison control; detrusor muscle; dietary; differential expression; disorder risk; egg; genetic analysis; genomic data; human old age (65+); improved; individualized medicine; metabolic profile; metabolomics; micturition urgency; neuroregulation; neurotransmission; non-alcoholic fatty liver; novel; older women; prevent; preventive intervention; response; trimethyloxamine; urinary

Project Summary: Urinary urgency incontinence (UUI) is one of the most common conditions to impact women, and older women, in particular. When comparing women with and without urgency incontinence, those with UUI have lower quality of life scores and higher rates of anxiety and depression. While the incidence and prevalence of UUI has been well studied, the pathophysiology of the disease is poorly understood. In the majority of cases, UUI is classified as idiopathic or “age- related”. In these cases, there are likely numerous genetic, environmental, dietary, metabolic and clinical factors and inter-factor interactions that lead to the development of UUI and these interactions likely center around the disturbance of normal neural signaling which controls micturition. Improving our understanding of how UUI develops in women without an overt clinical condition and how the cholinergic signaling system is involved will likely contribute to an individualized treatment paradigm for managing UUI as well as the development of novel treatments. In this proposal we will use the robust longitudinal data present in the Nurses’ Health Study (NHS) and NHS II to classify the plasma levels of cholinergic metabolites in women with and without. We will investigate whether non-cholinergic metabolites and single nucleotide polymorphisms for UUI lead to this condition and how interactions between these variables and cholinergic metabolites and clinical and demographic risk factors lead to the development of UUI. We will also evaluate how dietary choline impacts the presence of cholinergic metabolites, and whether this interaction is associated with expression of the UUI phenotype.

项目概要： 尿急性尿失禁（UUI）是影响女性的最常见疾病之一， 尤其是老年妇女。当比较有和没有急迫性尿失禁的女性时， UUI患者的生活质量评分较低，焦虑和抑郁的发生率较高。 虽然UUI的发病率和患病率已经得到了很好的研究，但UUI的病理生理学还没有完全阐明。 疾病知之甚少。在大多数情况下，UUI被归类为特发性或“年龄- 相关”。在这些情况下，可能有许多遗传，环境，饮食，代谢 以及导致UUI发展的临床因素和因素间相互作用， 相互作用可能围绕着正常神经信号的干扰， 排尿提高我们对UUI如何在没有明显临床表现的女性中发展的理解。 条件和如何胆碱能信号系统参与将可能有助于 管理UUI的个体化治疗范式以及新的 治疗。在本提案中，我们将使用护士报告中提供的稳健的纵向数据。 健康研究（NHS）和NHS II，对 女人有没有。我们将研究非胆碱能代谢物和单个 UUI的核苷酸多态性导致这种情况，以及这些基因之间的相互作用 变量和胆碱能代谢物以及临床和人口统计学风险因素导致 UUI的发展。我们还将评估饮食胆碱如何影响 胆碱能代谢物，以及这种相互作用是否与UUI的表达相关 表型