Intrauterine exposure to tobacco smoke, DNA methylation, and vision disorders in preschool children
学龄前儿童宫内烟草烟雾暴露、DNA 甲基化和视力障碍
基本信息
- 批准号:9803632
- 负责人:
- 金额:$ 41.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-01 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:African AmericanAgeAmblyopiaBilateralBiologicalBiological AssayBiological MarkersBiological ProcessBirthBloodBlood specimenCaliforniaChemicalsChildChildhoodCigaretteCorneaCotinineCytosineDNA MethylationDataDevelopmentDiseaseDisease OutcomeDoseEarly identificationElectronic Nicotine Delivery SystemsElectronic cigaretteEnvironmentEnvironmental Tobacco SmokeEpidemiologyEpigenetic ProcessEtiologyExposure toEye diseasesFetal DevelopmentFetusGenetic DiseasesGenetic studyGenomicsGuanineHealthHyperopiaImpairmentIndividualInheritedInvestigationKnowledgeLate pregnancyLengthLifeLightLinkLos AngelesLow Birth Weight InfantMeasuresMediatingMetabolismMethodsModificationMonitorMothersNeonatalNeonatal ScreeningNested Case-Control StudyNewborn InfantNicotineNot Hispanic or LatinoOutcomePatient Self-ReportPhenotypePlayPopulationPopulation HeterogeneityPopulation StudyPredispositionPregnancyPreschool ChildProviderPublic HealthRefractive ErrorsReportingResearchResourcesRetinal DiseasesRiskRisk FactorsRoleScientistSmokeSmokingSourceSpottingsStrabismusSusceptibility GeneSystems DevelopmentTestingThird Pregnancy TrimesterTobaccoTobacco smokeVariantVisionVision DisordersVisual Acuityagedbasecase controlcognitive functionearly childhoodearly screeningenvironmental tobacco smoke exposurefetalhigh riskimprovedin vivoinorganic phosphateinsightmaternal cigarette smokingneuron developmentnicotine replacementnovelpreventpublic health relevanceresponsescreeningscreening programsmoking during pregnancytooltreatment responseuptakevision developmentvisual motor
项目摘要
Project Summary
Vision disorders in early childhood, such as strabismus, amblyopia and high hyperopia, can significantly impair
the development of visual, motor, and cognitive functions. There is a need for better understanding of their
disease etiology which remains mostly unknown and methods for early identification of these disorders, which
still remain undetected in many children until their older ages when response to treatment is worse. Maternal
smoking during pregnancy (MSP), especially sustained smoking that persisted into third trimester, has been
consistently associated with several pediatric vision disorders including hyperopia, strabismus, and bilateral
amblyopia, and nicotine is considered as a key chemical responsible for the effects. The broad impact of MSP
on multiple vision disorders indicates that disturbance of intrauterine environment and fetal development may
play an important role in the development of vision disorders that occur very early in life. However, intrauterine
exposure to tobacco smoke or nicotine are not well captured by self-reported MSP, due to under-reporting,
exposure to overlooked sources of smoke or nicotine (e.g., environmental tobacco smoke, nicotine
replacement therapy), and variation in the uptake and metabolism of tobacco smoke by the mother and in the
fetal response to intrauterine disturbance. Objective and reliable measures of biologically effective dose of
intrauterine exposure to tobacco smoke or early biological effects of this exposure are needed. There have
been major advances in identifying specific genomic loci that are differentially methylated in newborns in
response to MSP and accumulating evidence linking alterations to DNA methylation at birth with childhood
diseases and outcomes such as low birth weight. These led us to hypothesize that epigenetic changes can
alter the development of the vision system in the fetus, leading to the development of vision disorders in early
childhood. To test this hypothesis, we propose to conduct a case-control study nested within the Multiethnic
Pediatric Eye Disease Study (MEPEDS) and retrieve neonatal dried blood spots (DBSs) that had been
collected by the California State’s Genetic Disease Screening Program from MEPEDS children at their birth.
Using these biospecimens, we will 1) assess the relationship of cotinine level in DBS and tobacco dosimeter
based on DNA methylation marks, in comparison to self-reported MSP, with strabismus, bilateral decreased
visual acuity, and hyperopia in 1508 preschool children; and 2) investigate epigenetic susceptibility loci for
hyperopia by comparing DNA methylation in neonatal DBS from 508 cases and an equal number of random
controls. Findings from this proposed study will have a great impact on assessing population and individual
risks from intrauterine exposure to different sources of tobacco smoke, understanding underlying biological
mechanisms, early screening of pediatric vision disorders, and preventing adverse impacts of these vision
disorders.
项目概要
儿童早期的视力障碍,如斜视、弱视和高度远视,会严重损害视力
视觉、运动和认知功能的发展。需要更好地了解他们
疾病的病因学仍然大多未知,以及早期识别这些疾病的方法,
在许多儿童中,直到年龄较大时,对治疗的反应较差时,这种疾病仍未被发现。产妇
怀孕期间吸烟(MSP),尤其是持续到妊娠晚期的持续吸烟,已成为
与多种儿童视力障碍(包括远视、斜视和双眼视力障碍)始终相关
弱视,尼古丁被认为是造成弱视的关键化学物质。 MSP 的广泛影响
对多种视力障碍的研究表明,宫内环境和胎儿发育的紊乱可能
在生命早期发生的视力障碍的发展中发挥着重要作用。然而,宫内
由于报告不足,自我报告的 MSP 未能很好地捕捉到接触烟草烟雾或尼古丁的情况,
暴露于被忽视的烟雾或尼古丁来源(例如环境中的烟草烟雾、尼古丁
替代疗法),以及母亲和孩子对烟草烟雾的吸收和代谢的变化
胎儿对宫内紊乱的反应。客观可靠的生物有效剂量测量
需要在宫内暴露于烟草烟雾或这种暴露的早期生物效应。有
在鉴定新生儿中差异甲基化的特定基因组位点方面取得了重大进展
对 MSP 的反应并积累出生时 DNA 甲基化改变与儿童期相关的证据
疾病和后果,例如低出生体重。这些使我们假设表观遗传变化可以
改变胎儿视觉系统的发育,导致早期视力障碍的发展
童年。为了检验这一假设,我们建议进行一项嵌套在多民族研究中的病例对照研究
小儿眼病研究 (MEPEDS) 并检索已检测到的新生儿干血斑 (DBS)
加利福尼亚州遗传疾病筛查计划从 MEPEDS 儿童出生时收集的数据。
使用这些生物样本,我们将 1) 评估 DBS 中可替宁水平与烟草剂量计的关系
基于 DNA 甲基化标记,与自我报告的 MSP 相比,斜视、双侧下降
1508 名学龄前儿童的视力和远视情况; 2) 研究表观遗传易感性位点
通过比较 508 例和同等数量的随机样本中新生儿 DBS 的 DNA 甲基化来了解远视
控制。这项拟议研究的结果将对评估人口和个人产生重大影响
子宫内暴露于不同来源的烟草烟雾的风险,了解潜在的生物学风险
机制,早期筛查儿科视力障碍,并预防这些视力的不利影响
失调。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Xuejuan Jiang其他文献
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- 批准号:
10745164 - 财政年份:2023
- 资助金额:
$ 41.25万 - 项目类别:
Intrauterine exposure to tobacco smoke, DNA methylation, and vision disorders in preschool children
学龄前儿童宫内烟草烟雾暴露、DNA 甲基化和视力障碍
- 批准号:
10669723 - 财政年份:2019
- 资助金额:
$ 41.25万 - 项目类别:
Intrauterine exposure to tobacco smoke, DNA methylation, and vision disorders in preschool children
学龄前儿童宫内烟草烟雾暴露、DNA 甲基化和视力障碍
- 批准号:
10000978 - 财政年份:2019
- 资助金额:
$ 41.25万 - 项目类别:
Intrauterine exposure to tobacco smoke, DNA methylation, and vision disorders in preschool children
学龄前儿童宫内烟草烟雾暴露、DNA 甲基化和视力障碍
- 批准号:
10220040 - 财政年份:2019
- 资助金额:
$ 41.25万 - 项目类别:
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