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: 8919433
• 负责人: HYOSHIN KIM
• 金额: $ 16.47万
• 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/8919433
• 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; Health; 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; 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; cognitive performance; disorder control; disorder risk; improved; interest; male; meetings; mitochondrial dysfunction; 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(申请人提供)：这项拟议的研究将评估五种卟啉的血浆和尿液浓度，它们是人类细胞线粒体内产生的化学物质，是自闭症谱系障碍(ASD)的早期生物标志物。线粒体功能障碍被认为与ASD有关。此外，ASD的早期诊断和干预可以改善儿童的认知表现、语言技能和适应行为。这是公共卫生的目标 该项目的一部分是，拟议的生物标记物将有助于将儿童识别为ASD评估的候选对象，从而导致对这些儿童进行更早的干预，并可能改善这些儿童的生活质量。这项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与环境风险(CHARE)研究的受试者。受试者年龄在24到60个月之间，登记在Charge研究中，将包括总共828名儿童，356名ASD儿童，323名认知和/或适应功能(DD)非ASD发育迟缓儿童作为阳性对照，149名典型发育(TD)儿童作为正常对照。从电荷研究保存的冷冻标本中获得等量的血浆和/或尿液，并将使用高压液相色谱和串联质谱仪(HPLC-MS/MS)对五种卟啉进行检测。该项目的目的是结合Logistic回归和受试者操作特征(ROC)分析，证明与TD对照相比，这些卟啉可用于识别高达20%-33%的ASD病例，其特异度为98%。类似的分析将对自闭症病例(符合和不符合发育迟缓标准的人)以及没有自闭症的发育迟缓儿童进行类似的分析。我们将在分析中包括对社会经济地位、种族和其他协变量的衡量，并评估年龄和性别如何影响敏感度和特异度。由于已经收集了数据和样本，我们建议进行的研究的效率将会很高。