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（由申请人提供）：拟议的研究将评估五个卟啉的血浆和尿液浓度，即人类细胞线粒体内产生的化学物质，作为自闭症谱系障碍（ASD）的早期生物标志物（ASD）。线粒体功能障碍与ASD有关。此外，ASD的早期诊断和干预可以提高孩子的认知表现，语言技能和适应性行为。这是公共卫生目标 在该项目中，拟议的生物标志物将有助于将儿童识别为ASD评估的候选人，从而导致较早的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利福尼亚大学儿童环境健康中心的遗传学和环境（Charge）研究的儿童自闭症风险（Charge）研究的受试者。受试者，全部24至60个月大，并参加了指控研究，将包括828名儿童，356名ASD，323个，323个患有认知和/或自适应功能（DD）的非ASD发育延迟（DD）用作阳性对照，以及149名通常用作正常对照的儿童。从电荷研究维持的冷冻样品中获得血浆和/或尿液的等分试样，并将使用高压液相色谱和串联质谱法（HPLC-MS/MS）对五个卟啉进行测试。该项目的目的是使用逻辑回归和接收器操作特征（ROC）分析的组合证明这些卟啉可用于识别与TD对照相比，特异性为98％的ASD案例中最多可识别20-33％。将对ASD病例的子集（那些和不符合发育延迟标准的人）以及没有ASD的DD儿童进行类似的分析。我们将在分析中包括SES，种族和其他协变量的度量，并评估年龄和性别如何影响敏感性和特异性。由于已经收集了数据和标本，因此我们提出的研究的效率将非常高。