Evaluating Plasma and Urine Porphyrins as Biomarkers of ASD

评估血浆和尿液卟啉作为 ASD 的生物标志物

• 批准号: 8772610
• 负责人: Nicholas J. Heyer
• 金额: $ 25.1万
• 依托单位: BATTELLE CENTERS/PUB HLTH RES & EVALUATN
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8772610
• 关键词: Accounting; Adaptive Behaviors; Age; Age-Months; Aliquot; Attention; Autistic Disorder; Behavior; Biological Markers; California; Case-Control Studies; Cells; Chemicals; Child; Childhood; Clinical; Clinical Data; Cognitive; Collaborations; Collection; DNA copy number; Data; Data Set; Developmental Delay Disorders; Diagnosis; Early Diagnosis; Early Intervention; Enrollment; Environment; Environmental Health; Ethnic Origin; Etiology; Freezing; Gender; Genetic; Genetic Risk; Goals; Heme; High Pressure Liquid Chromatography; Human; Hyperactive behavior; Intervention; Korea; Koreans; Laboratories; Language; Learning; Link; Logistic Regressions; Measures; Mitochondria; Mitochondrial DNA; Neurodevelopmental Disorder; Outcome; Parental Ages; Participant; Pathway interactions; Pentas; Performance; Pilot Projects; Plasma; Porphyrins; Public Health; Publishing; Quality of life; Race; Receiver Operating Characteristics; Recruitment Activity; Regression Analysis; Reporting; Research Personnel; Resources; Risk; Sensitivity and Specificity; Severities; Socioeconomic Status; Specificity; Specimen; Techniques; Testing; United States National Institutes of Health; Universities; Urine; aged; autism spectrum disorder; base; disorder control; disorder risk; improved; interest; male; meetings; mitochondrial dysfunction; public health relevance; skills; tandem mass spectrometry; urinary

DESCRIPTION (provided by applicant): The proposed study will evaluate the plasma and urinary concentrations of five porphyrins, chemicals produced within the mitochondria of human cells, as early biomarkers of autism spectrum disorder (ASD). Mitochondrial dysfunction has been implicated in ASD. Furthermore, early diagnosis and intervention in ASD can improve the child's cognitive performance, language skills, and adaptive behavior. It is the public health goal of this project that the proposed biomarker will help identify children as candidates for ASD assessment, leading to earlier intervention and potentially improved quality of life for these children. The proposed study will use subjects from the Childhood Autism Risks from Genetics and Environment (CHARGE) study based at the University of California at Davis' Center for Children's Environmental Health. Subjects, all between 24 and 60 months of age and enrolled in the CHARGE study, will include a total of 828 children, 356 with ASD, 323 with non-ASD developmental delays in cognitive and/or adaptive function (DD) used as positive controls, and 149 typically developing (TD) children used as normal controls. Aliquots of plasma and/or urine will be obtained when available from frozen specimens maintained by the CHARGE study, and will be tested for the five porphyrins using high pressure liquid chromatography and tandem mass spectrometry (HPLC-MS/MS). The aims of this project are to demonstrate, using a combination of logistic regression and receiver operating characteristic (ROC) analysis, that these porphyrins can be used to identify up to 20-33% of ASD cases with a specificity of 98% compared to TD controls. Similar analyses will be conducted on subsets of ASD cases (those who do and do not meet the criteria for developmental delay), as well as the DD children without ASD. We will include measures of SES, ethnicity and other covariates in our analyses, and evaluate how age and gender influence sensitivity and specificity. As the data and specimens have already been collected, the efficiency of our proposed study would be very high.

描述（由申请人提供）：拟议的研究将评估五种卟啉（人类细胞线粒体内产生的化学物质）的血浆和尿液浓度，作为自闭症谱系障碍（ASD）的早期生物标志物。线粒体功能障碍与自闭症谱系障碍有关。此外，自闭症谱系障碍的早期诊断和干预可以改善孩子的认知表现、语言技能和适应行为。这是公共卫生目标 该项目认为，拟议的生物标志物将有助于识别儿童作为自闭症谱系障碍评估的候选者，从而实现早期干预并可能改善这些儿童的生活质量。拟议的研究将使用加州大学戴维斯分校儿童环境健康中心的儿童自闭症遗传和环境风险（CHARGE）研究的受试者。参加 CHARGE 研究的受试者年龄均在 24 至 60 个月之间，总共包括 828 名儿童，其中 356 名患有 ASD，323 名患有认知和/或适应功能 (DD) 发育迟缓的非 ASD 儿童，用作阳性对照，以及 149 名典型发育 (TD) 儿童用作正常对照。当可从 CHARGE 研究保存的冷冻样本中获得等份血浆和/或尿液时，将使用高压液相色谱和串联质谱 (HPLC-MS/MS) 检测五种卟啉。该项目的目的是通过结合逻辑回归和接受者操作特征 (ROC) 分析，证明这些卟啉可用于识别高达 20-33% 的 ASD 病例，与 TD 相比，特异性为 98%控制。类似的分析还将针对自闭症谱系障碍 (ASD) 病例子集（符合或不符合发育迟缓标准的儿童）以及不患有自闭症谱系障碍 (ASD) 的 DD 儿童进行。我们将在分析中纳入社会经济地位、种族和其他协变量的衡量标准，并评估年龄和性别如何影响敏感性和特异性。由于数据和标本已经收集完毕，我们提出的研究效率会非常高。