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

基本信息

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
项目类别：
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&apos 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&apos 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

项目摘要

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：急迫性尿失禁（UUI）是影响女性的最常见病症之一，和老年女性，特别是在比较有和没有急迫性尿失禁的女性时，患有 UUI 的人生活质量得分较低，焦虑和抑郁的比例较高。虽然 UUI 的发病率和患病率已得到充分研究，但其病理生理学在大多数情况下，UUI 被归类为特发性或“年龄相关性疾病”。在这些情况下，可能有许多遗传、环境、饮食、代谢方面的因素。导致 UUI 发展的临床因素和因素间相互作用相互作用可能集中在控制正常神经信号传导的干扰上提高我们对女性 UUI 如何在没有明显临床表现的情况下发生的了解。条件以及胆碱能信号系统如何参与可能有助于用于管理 UUI 的个体化治疗范式以及新型药物的开发在本提案中，我们将使用护士的可靠纵向数据。健康研究 (NHS) 和 NHS II 对胆碱能代谢物的血浆水平进行分类我们将调查是否有非胆碱能代谢物和单一的女性。 UUI 的核苷酸多态性导致这种情况，以及它们之间的相互作用如何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我们还将评估膳食胆碱如何影响 UUI 的存在。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。