GOUTY DIATHESIS--PATHOPHYSIOLOGY AND MOLECULAR GENETIC BASIS

痛风素质--病理生理学和分子遗传学基础

• 批准号: 6564154
• 负责人: KHASHAYAR SAKHAEE
• 金额: $ 22.85万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-01 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6564154
• 关键词: acidity /alkalinity; ammonia; clinical research; genetic susceptibility; gout; human subject; insulin sensitivity /resistance; medical complication; nephrocalcinosis; pathologic process; urate; urinalysis; urinary calculi

Description: (Taken directly from the application) A disturbance in urate metabolism has been shown to lead to the development of both uric acid and calcium stones. In addition, primary gout is frequently observed with uric acid lithiasis, where undue urinary pH from defective ammonium production is believed to promote uric acid crystallization. We have used the term gouty diathesis to describe stone formation associate with primary gout, and that it is comprised of acquired and primary (genetic) variants. This hypothesis will be tested by (1) assessing whether defective ammonium production in gouty diathesis is evident by controlling acid intake and imposing phosphate restriction and that, in the acquired form of the disease, insulin resistance is responsible for undue acidity and other biochemical features of this disease, and (2) identifying the molecular defect in the "primary" genetic form of the disease. These studies will help elucidate the pathophysiology of gouty diathesis and may lead to improvements in the diagnosis and treatment of this form of urolithiasis.

产品描述：（直接取自应用）尿酸盐代谢紊乱已被证明会导致尿酸和钙结石的发展。此外，原发性痛风经常与尿酸结石一起观察到，其中来自有缺陷的铵产生的不适当的尿液pH被认为促进尿酸结晶。我们用痛风素质这个术语来描述与原发性痛风相关的结石形成，它由获得性和原发性（遗传）变异组成。这一假设将通过以下方式进行检验：（1）通过控制酸摄入量和限制磷酸盐来评估痛风素质中的氨生成缺陷是否明显，以及在获得性疾病中，胰岛素抵抗是否是导致该疾病酸度过高和其他生化特征的原因，以及（2）鉴定该疾病“原发”遗传形式中的分子缺陷。这些研究将有助于阐明痛风素质的病理生理学，并可能导致这种形式的尿石症的诊断和治疗的改进。