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研究生:柯晨鍾
研究生(外文):Chen-Chung Ko
論文名稱:臍帶血鉛、VDR-FokI多型性與兒童兩歲的神經發展
論文名稱(外文):Lead in umbilical cord blood, VDR-FokI polymorphism and children’s neurodevelopment at the age of two years
指導教授:陳保中陳保中引用關係
指導教授(外文):Pau-Chung Chen
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:職業醫學與工業衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文出版年:2007
畢業學年度:96
語文別:英文
論文頁數:52
中文關鍵詞:神經行為發展嬰幼兒綜合發展測驗real-time PCR
外文關鍵詞:leadneurobehavioral developmentComprehensive Developmental Inventory for Infants and Toddlers (CDIIT)real-time PCR
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鉛暴露會對兒童的成長發育造成影響,尤其是神經系統方面,而近年來在許多流行病學的研究中,也發覺到不同的基因多型性在暴露到疾病的發生之過程中扮演著關鍵的角色,但是對於基因易感受性族群,尤其是胎兒成長發育的研究仍然缺乏,本篇的研究目的是探討Vitamin D Receptor基因多型性在臍帶血鉛暴露與兒童早期神經行為發展的影響。本研究對象來自「台灣出生世代研究」中,於孕婦生產時蒐集孕婦的血液與新生兒臍帶血,利用感應耦合電漿質譜分析儀(ICP-MS)進行懷孕期間鉛的暴露評估,並以問卷調查相關的干擾因子。於出生6個月與24個月後利用「嬰幼兒綜合發展測驗」,來評估新生兒的神經行為發展,並利用家庭環境評估量表評估兒童教養環境。基因多型性的分析以鉛毒性相關的Vitamin D Receptor基因為研究重點,利用real-time-PCR方法分析其基因多型性。研究族群平均血鉛濃度1.3 ug/dl,而各VDR FokI基因比例,TT佔21%, CT 佔54%,CC佔25 %。統計分析結果發現,高血鉛暴露(> 1.64 ug/dl)時,幼兒2歲的認知發展分數比低血鉛暴露(<= 1.64 ug/dl)下降5.85分,而在基因多型性方面,高血鉛暴露且具VDR FokI基因多型性兒童的社會領域發展分數比低血鉛暴露且無VDR FokI基因多型性兒童低6.83分,而在語言領域發展,不論血鉛濃度高低,VDR FokI基因多型性都有影響。因此,VDR FokI基因多型性可能會使得兒童神經行為的發展對鉛毒性感受性產生差異。
Lead may produce adverse effects on the nervous system and influence cognition, memory and intelligence. Even with low dose exposure, lead may still have adverse effects on humans, especially infants and pregnant women. Genetic polymorphism may play an important role in modulating the health effects, but there have been few studies about the relation between genetic polymorphism and infant neurobehavioral development. The objective of this study was to explore the modifier effect of VDR FokI polymorphism on lead exposure and early childhood neurodevelopment.
Our study subjects were pregnant women and their neonates in the pilot study of Taiwan Birth Panel Study (TBPS) conducted between April 2004 and January 2005. We collected neonatal umbilical cord blood at delivery for lead analysis. The cord blood lead concentration was detected by ICP-MS. We obtained information on relevant confounding factors by personal interview based on a structured questionnaire. The Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT) and Infant/Toddler HOME of Home Observation for Measurement of the Environment Inventory (IT-HOME) were used to evaluate infant neurobehavioral development at six months of age. The second evaluation was performed when children were twenty-four months of age. VDR genetic polymorphisms were analyzed by real-time PCR method. The mean cord blood lead levels was 1.3 ug/dl and the VDR FokI genetic type rates were 21% for TT, 54% for CT and 24% for CC. Subjects with high lead exposure (> 1.64 ug/dl) had lower 5.85 scores in cognitive domain than subjects with low lead exposure (<= 1.64 ug/dl). Further, our analyses suggest that as cord blood lead increased, the scores of children with CT and CC genotype declined significantly (6.83 scores) in social domain compared with children who carried TT genotype. However, language scores were significantly lower in children with VDR FokI polymorphism regardless of lead levels. Overall, VDR FokI polymorphism may have a modifier effect on the neurobehavioral development of children who have lead toxicity.
摘要 I
Abstract Ⅲ
Contents Ⅴ
List of table Ⅵ
Introduction 1
Materials and Methods 4
Study design and population 4
Medical records and questionnaire data 5
Neurobehavioral development measurements 6
Laboratory analysis 8
Lead levels analysis 8
DNA preparation and genetic polymorphism analysis 8
Sequence analysis 10
Covariates 10
Statistical analysis 12
Results 14
Discussion 16
Conclusion 22
Reference 23
Appendix 38
Lead and neurobehavioral development 38
Lead and genetic polymorphism 44
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