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

项目总结： 尿失禁(UUI)是影响女性的最常见疾病之一， 尤其是年长的女性。当比较患有和不患有尿失禁的女性时， UUI患者的生活质量得分较低，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 人们对疾病知之甚少。在大多数情况下，UUI被归类为特发性或“年龄- 有关“。在这些情况下，可能有许多遗传、环境、饮食、代谢 以及临床因素和因素间的相互作用导致UUI的发展以及这些 相互作用可能集中在控制正常神经信号的干扰上 排尿。提高我们对无明显临床表现的女性尿路感染发生的了解 情况以及胆碱能信号系统是如何参与的可能会有助于 UUI管理的个体化治疗范式及小说的发展 治疗。在这项建议中，我们将使用在护士的 健康研究(NHS)和NHS II对老年人血浆胆碱能代谢物水平进行分类 有没有没有的女人。我们将调查非胆碱能代谢物和单一 UUI的核苷酸多态导致这种情况，以及它们之间的相互作用 变量和胆碱能代谢物以及临床和人口学危险因素导致 UUI的发展。我们还将评估饮食中的胆碱如何影响 胆碱能代谢物，以及这种相互作用是否与UUI的表达有关 表型。

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.