STEROL METABOLISM & DIETARY CHOLESTEROL IN SLO SYNDROME

甾醇代谢

• 批准号: 6084732
• 负责人: WILLIAM E CONNOR
• 金额: $ 17.96万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6084732
• 关键词: blood chemistry; child (0-11); cholanate compound; cholesterol; cholesterol ester storage disease; clinical research; clinical trials; congenital disorders; developmental nutrition; diet therapy; dietary lipid; enzyme feedback; enzyme mechanism; gastrointestinal absorption /transport; genetic screening; human genetic material tag; human subject; human therapy evaluation; micrencephaly; molecular genetics; nutrition related tag; oxidoreductase; pediatrics; steroid metabolism; urinalysis

In Smith-Lemli-Opitz Syndrome (SLOS) cholesterol levels in plasma and tissue are low, and concentrations of 7-dehyrdocholesterol and other sterols are high. These other sterols are pathologic and are not normally present. Patients with SLOS block the synthesis of cholesterol because of a deficiency in enzyme 7-dehydrocholesterol delta 7-reductase, and it is 7-dehydrocholesterol that converts to cholesterol in the last step of cholesterol synthesis. The principal investigator (PI) has proposed to feed dietary cholesterol from three different sources, egg yolk, crystalline cholesterol and butterfat to SLOS patients. Cholesterol absorption and synthesis will be determined in both very low cholesterol diets and high cholesterol diets. Using three different techniques, the PI will measure whole body cholesterol absorption and synthesis as well as bile acid synthesis in SLOS patients and in control subjects. The three different techniques include measuring cholesterol synthesis and absorption and bile acid synthesis by the sterol balance, determining cholesterol synthesis by measuring the incorporation of deuterated water into erythrocyte cholesterol, and determining sterol synthesis in SLOS patients and control subjects by measuring 24-hour urinary mevalonate excretion. The objective is to fully understand the effects that 7-dehydrocholesterol delta 7-reductase deficiency has on sterol metabolism in SLOS. Long-term dietary cholesterol supplementation feeding studies might produce more definitive results about the effect that 7-dehydrocholesterol delta 7-reductase deficiency has on sterol metabolism than have short-term supplementation feeding studies. Once the optimal dose and best source of dietary cholesterol (egg yolk, crystalline cholesterol or butterfat) is determined, the diets of SLOS patients will be supplemented for one year or longer. Biochemical parameters of these patients will be measured during this time. As a result of these feeding studies, therapies can be devised and applied to SLOS patients immediately following identification of their condition. It is the PI's plan to identify mutations in the 7-dehydrocholesterol delta 7-reductase gene in SLOS patients in order to establish a genotype-phenotype correlation based on dysmorphology and sterol synthesis. Developmental testing will be performed.

在血浆中的Smith-Lemli-Opitz综合征（SLO）胆固醇水平 组织和组织较低，浓度为7-二胆胆固醇和其他 固醇高。这些其他固醇是病理性的，通常不是 展示。 SLO的患者阻止了胆固醇的合成 酶7-脱氢胆固醇三角洲7-还原酶的不足，它是 7-脱氢胆固醇在最后一步转化为胆固醇 胆固醇合成。首席研究员（PI）提出了进食 来自三种不同来源的饮食胆固醇，蛋黄，结晶 胆固醇和黄油对SLOS患者。胆固醇吸收和 合成将在非常低的胆固醇饮食和较高的水中确定 胆固醇饮食。使用三种不同的技术，PI将测量整体 体内胆固醇的吸收和合成以及胆汁酸合成 SLOS患者和对照受试者。这三种不同的技术包括 测量胆固醇的合成和吸收以及胆汁酸合成 固醇平衡，通过测量胆固醇的合成来确定胆固醇 将氘化的水掺入红细胞胆固醇中，并确定 通过测量24小时，SLOS患者和对照对象的固醇合成 泌尿甲酸盐排泄。目的是充分了解效果 7-脱氢胆固醇三角洲7-还原酶缺乏对固醇代谢有 在slos中。长期饮食胆固醇补充剂可能 关于7-脱氢胆固醇的影响产生更确定的结果 三角洲7-还原酶缺乏对固醇代谢的缺乏症比短期 补充喂养研究。曾经是最佳剂量和最佳来源 饮食中胆固醇（蛋黄，结晶胆固醇或黄油）是 确定，SLOS患者的饮食将补充一年或 更长。在此期间将测量这些患者的生化参数 时间。由于这些喂养研究，可以设计疗法，并 鉴定其后，立即应用于SLOS患者 健康）状况。 PI的计划是确定该突变 SLOS患者中的7-脱氢胆固醇三角洲7-还原酶基因 建立基于畸形和固醇的基因型 - 表型相关性 合成。将进行发展测试。