臺灣博碩士論文加值系統

長期追蹤一群鉛作業勞工(530位)，利用從民國86年至91年共6年的健康檢查資料包括：血鉛值、血中肌酸酐值、血中尿酸值、血壓值等，及問卷收集相關資料控制干擾因子；並且從血液中萃取DNA，利用聚合酵素連鎖反應及限制片段長度多型性分析的方法，定義ACE I/D及a-adducin G460W基因型；探討長期鉛作業工人的腎功能與血壓變化在不同基因型的表現，並進一步研究它們的交互作用。
這一群勞工91年時共有520人，男性佔59 %、平均年齡43（SD=7.9）歲、平均年資13（SD=7.8）年、平均收縮壓123 mmHg、平均舒張壓77 mmHg、平均血中肌酸酐0.95 mg/dL、平均血中尿酸6.37 mg/dL、平均血鉛值22 mg/dL，ACE的基因型II192（42%）人、DI116（26%）人、DD144（32%）人，a-adducin的基因型GG124（28%）人、GW235（53%）人、WW88（19%）人。在腎功能方面，以Mixed model分析控制年齡、性別、身體質量指數、吸煙習慣後，發現ACE I/D基因型可以影響血鉛對血中肌酸酐和肌酸酐清除率的作用；以Mixed model分析控制年齡、性別、身體質量指數、吸煙習慣後，發現血鉛會影響血中尿酸值；在血壓方面，以Mixed model分析控制年齡、性別、身體質量指數、吸煙習慣後，發現ACE I/D、a-adducin G460W基因型和血鉛都不會影響血壓值。
不同的ACE I/D基因型可能會影響鉛對腎功能的毒性，但有關的機轉不明，有待其他研究進一步探討。

We followed up a group of lead workers (n=530) from 1997 to 2002. The health examination data consisted of: blood lead levels, serum creatinine and uric acid levels, blood pressure levels. A questionnaire was used to collect potential confounder in the health examination. DNA was isolated from the whole blood of each worker. The ACE I/D and a-adducin G460W polymorphism are investigated by polymerase chain reaction and restriction fragment length polymorphism amplification of genomic DNA to define the The ACE I/D and a-adducin G460W genotypes. The main purpose of this study is to investigate the association among the different ACE I/D and a-adducin G460W genotypes to the renal functions and blood pressure in long-term lead exposed workers. The interaction of lead and gene polymorphism on renal functions and blood pressure was also evaluated in this study.
In 2002, totally 530 lead workers were recruited. Of them, 312（59%）were men. The average age was 43（SD=7.9）years, and , mean working duration was 13（SD=7.8）years. Among them, blood pressure（mean systolic pressure: 123 mmHg; mean diastolic pressure: 77 mmHg）, renal function tests（mean creatinine: 0.95 mg/dL）, uric acid（mean: 6.37 mg/dL）were found. Their average blood lead level was 22 mg/dL. ACE I/D genotypes distributed as II: 192（42%） people, DI: 116（26%） people, II: 144（32%） people. a-adducin G460W genotypes distributed as GG: 124（28%）people, GW: 235（53%）people, WW: 88（19%）people. Regarding renal functions using general linear mixed models analyses with adjustment of age, gender, body mass index, smoking habit, we found that the interaction of blood lead levels and ACE I/D types associated to serum creatinine levels and creatinine clearance rate. The analyses of uric acid levels with general linear mixed models found that blood lead levels significantly related with serum uric acid levels after adjusting the confounders. For blood pressures by general linear mixed models analyses with adjustment of age, gender, body mass index, smoking habit, there was no relation between blood pressure levels and ACE I/D, a-adducin G460W genotypes, blood lead levels.
In conclusion, the toxicity of lead to renal function may be affected by differential ACE I/D genotypes. Further studies and further assessment are clearly needed.

第一章 文獻探討
1.1 鉛對腎功能的影響 1
1.2 鉛對血壓的影響 4
1.3 ACE I/D及a-adducin G460W基因多型性對腎功能及血壓的影響 5
1.3.1 ACE I/D 5
1.3.2 a-adducin G460W 7
1.4 研究目的 8
第二章 研究方法
2.1 方法概述 9
2.2 研究對象 9
2.3 健康檢查 9
2.4 問卷 10
2.5 基因型分析 10
2.5.1 血液收集 10
2.5.2 Genomic DNA萃取 10
2.5.3 ACE I/D polymorphism 11
2.5.4 a-adducin G460W polymorphism 12
2.5.5實驗室實驗品質控制 13
2.6 統計分析方法 13第三章 兩家工廠基本資料的比較
3.1 基本資料 15
3.2 健康檢查結果和ACE I/D基因型之相關性分析 15
3.3 健康檢查結果和a-adducin G460W基因型之相關性分析 16
第四章 長期鉛暴露對腎功能的影響
4.1 血中肌酸酐的Mixed Models結果 18
4.2 肌酸酐清除率的Mixed Models結果 19
第五章 長期鉛暴露對尿酸的影響
5.1 尿酸的Mixed Models結果 22
第六章 長期鉛暴露對血壓的影響
6.1 收縮壓的Mixed Models結果 24
6.2 舒張壓的Mixed Models結果 25
第七章 討論 27
參考文獻 32
附表
表3之1 兩家工廠2002年健康檢查結果 38
表3之2 兩家工廠歷年血鉛值在不同ACE I/D基因型的比較 39
表3之3 兩家工廠歷年血中肌酸酐值在不同ACE I/D基因型的比較 40
表3之4 兩家工廠歷年血中尿酸值在不同ACE I/D基因型的比較 41
表3之5 兩家工廠歷年收縮壓在不同ACE I/D基因型的比較 42
表3之6 兩家工廠歷年舒張壓在不同ACE I/D基因型的比較 43
表3之7 兩家工廠歷年血鉛值在不同a-adducin G460W基因型的比較 44
表3之8 兩家工廠歷年血中肌酸酐值在不同a-adducin G460W基因型的比較 45
表3之9 兩家工廠歷年血中尿酸值在不同a-adducin G460W基因型的比較 46
表3之10 兩家工廠歷年收縮壓在不同a-adducin G460W基因型的比較 47
表3之11 兩家工廠歷年舒張壓在不同a-adducin G460W基因型的比較 48
表4之1 血鉛、ACE I/D或a-adducin G460W基因多型性對血中肌酸酐的影響，在控制年齡、性別、BMI、抽菸習慣後之Mixed Model分析結果 49
表4之2 血鉛與年齡、ACE I/D或a-adducin G460W基因多型性的交互作用對血中肌酸酐的影響，在控制性別、BMI、抽菸習慣後之Mixed Model分析結果 50
表4之3 血鉛、ACE I/D或a-adducin G460W基因多型性對肌酸酐清除率的影響，在控制年齡、性別、BMI、抽菸習慣後之Mixed Model分析結果 51表4之4 血鉛與年齡、ACE I/D或a-adducin G460W基因多型性的交互作用對肌酸酐清除率的影響，在控制性別、BMI、抽菸習慣後之Mixed Model分析結果 52
表5之1 血鉛、ACE I/D或a-adducin G460W基因多型性對血中尿酸的影響，在控制年齡、性別、BMI、CCR、抽菸習慣後之Mixed Model分析結果 53
表5之2 血鉛與年齡、ACE I/D或a-adducin G460W基因多型性的交互作用對血中尿酸的影響，在控制性別、BMI、CCR、抽菸習慣後之Mixed Model分析結果 54
表6之1 血鉛、ACE I/D或a-adducin G460W基因多型性對收縮壓的影響，在控制年齡、性別、BMI、CCR、抽菸習慣後之Mixed Model分析結果
55
表6之2 血鉛與年齡、ACE I/D或a-adducin G460W基因多型性的交互作用對收縮壓的影響，在控制性別、BMI、CCR、抽菸習慣後之Mixed Model分析結果 56
表6之3 血鉛、ACE I/D或a-adducin G460W基因多型性對舒張壓的影響，在控制年齡、性別、BMI、CCR、抽菸習慣後之Mixed Model分析結果
57
表6之4 血鉛與年齡、ACE I/D或a-adducin G460W基因多型性的交互作用對舒張壓的影響，在控制性別、BMI、CCR、抽菸習慣後之Mixed Model分析結果 58
附圖
圖1 鉛對腎臟急性及慢性的影響 2
圖2 Phosphoribosylation of hypoxanthine and guanine to from IMP and GMP, respectively. Both reactions are catalyzed by hypoxanthine-guanine phosphoribosyltransferase. 4
圖3 ACE I/D基因多型性電泳分析 11
圖4 a-adducin G460W基因多型性電泳分析 13
圖5 歷年血鉛變化情形 28
圖6 歷年肌酸酐變化情形 28
圖7 歷年尿酸變化情形 29
圖8 歷年收縮壓變化情形 30
圖9 歷年舒張壓變化情形 31

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