鉛與基因多型性的交互作用對長期鉛暴露工人腎功能與血壓影響之研究

Interaction of lead and gene polymorphism on renal function and blood pressure in long-term lead exposed workers.

孫千雯(Chien-Wen Sun)

指導教授 ： 何啟功 ； 莊弘毅 ； 戴明泓

高雄醫學大學/健康科學院/職業安全衛生研究所/碩士(2003年)

摘要

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。

關鍵字

鉛 ； 基因多型性 ； ACE I/D ； alpha-adducin G460W

並列摘要

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.

並列關鍵字

lead ； genetic polymorphism ； angiotensin-converting enzyme insertion/deletion ； alpha-adducin Gly460Trp

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