Epidemiological Research on Autism in Jamaica - Phase II

描述(由申请人提供)：自闭症谱系障碍(ASD)是一种复杂的终生神经发育和行为障碍，表现在婴儿期或幼儿期，特征是社交和沟通障碍，以及重复的、刻板印象的行为。尽管ASD的原因尚不清楚，但有证据表明，其起源很可能是发生在子宫或婴儿早期的基因-环境相互作用的结果。该项目的长期目标是扩大我们在牙买加进行大规模基于人群的自闭症研究的能力。在过去的2-3年里，在NICHD/FIC(R21 HD057808；PI：RAHBAR)的资助下，我们德克萨斯大学休斯顿健康科学中心的研究团队与牙买加西印度群岛大学的Maureen Samms-Vaughan博士和她的同事合作，研究了谷胱甘肽-S-转移酶(Gst)基因和五种重金属(铅、汞、砷、镉、锰)在ASD中的作用。在拟议的项目中，我们将评估从2011年牙买加出生队列登记的144名新生儿分离的脐带血中多氯联苯(PCbs)和有机氯(OC)杀虫剂的水平，以检验牙买加儿童在宫内接触这些化学物质的假设，并确定与这些暴露相关的因素。此外，我们将进行一项年龄和性别匹配的病例对照研究(240对配对)，以调查环境暴露于多氯联苯和有机碳杀虫剂是否在ASD中起作用。此外，我们将评估GST基因的特定多态(GSTM1、GSTT1、GSTP1)的作用，以及它们与这些OCS之间潜在的相互作用与ASD的关系。对于病例和对照，我们都将进行问卷调查，以评估父母的人口统计和社会经济地位、职业、吸烟和饮酒状况。此外，还将收集有关发育障碍的家族史、家庭规模、指标儿童的出生顺序以及该儿童是否正在服用任何药物的信息。此外，还将进行饮食问卷调查，以了解可能接触多氯联苯和有机碳杀虫剂等环境污染物的情况。在访谈结束时，将从病例和对照儿童中收集1-2毫升的唾液和大约4-5毫升的血清。DNA分离和多态分析将在德克萨斯大学公共卫生学院人类遗传学中心进行。血清样本将由位于密歇根州兰辛市的密歇根州社区卫生部门化学和毒理学部门的CDC认证实验室使用毛细管柱气相色谱分析209种多氯联苯中的92种和18种有机碳农药。

DESCRIPTION (provided by applicant): Autism Spectrum Disorders (ASDs) are complex lifelong neurodevelopmental and behavioral disorders manifesting in infancy or early childhood, characterized by impairments in social interaction and communication, and by repetitive, stereotyped behavior. Although the causes of ASD are unknown, the evidence suggests that the origins are likely the result of gene- environment interaction occurring in utero or very early in infancy. The long term goal of this project is to expand our capacity for conducting large scale population-based ASD studies in Jamaica. During the past 2-3 years, with funding from NICHD/FIC (R21 HD057808; PI: Rahbar) our research team at the University of Texas Health Science Center at Houston (UTHealth) has collaborated with Dr. Maureen Samms-Vaughan and her colleagues at the University of the West Indies (UWI) in Jamaica to investigate the role of the glutathione-S-transferase (GST) genes and five heavy metals (lead, mercury, arsenic, cadmium, manganese) in relation to ASD. In the proposed project, we will assess the levels of polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides in the cord-blood isolated from 144 newborns enrolled in the 2011 Jamaican birth cohort to test the hypothesis that children in Jamaica are exposed in utero to these chemicals and identify factors associated with such exposures. In addition, we will conduct an age- and sex-matched case-control study (240 matched pairs) to investigate whether environmental exposures to PCBs and OC pesticides play a role in ASD. Furthermore, we will assess the role of select polymorphisms in GST genes (GSTM1, GSTT1, GSTP1), and their potential interactions with these OCs in relation to ASD. For both cases and controls we will administer a questionnaire to assess the demographic and socioeconomic position, occupation, smoking and drinking status of the parents. In addition, information about family history of developmental disorders, family size, birth order of the index child and whether the child is taking any medications will be collected. Moreover, a dietary questionnaire aimed at capturing possible exposure to environmental contaminants such as PCBs and OC pesticides will be administered. At the end of interview, 1-2 mLs of saliva and about 4-5 mLs of serum will be collected from the case and control children. The DNA isolation and analysis of polymorphisms will be conducted at the Center for Human Genetics at UT School of Public Health. Serum samples will be analyzed for 92 of the 209 PCBs congeners and 18 OC pesticides using capillary column gas chromatography by a CDC-certified lab at the Division of Chemistry and Toxicology at Michigan Department of Community Health in Lansing, Michigan.