鉛作業勞工ALAD基因多型性與ALAD酵素活性及血液相關指標之探討

The relationship between genetic polymorphism of ALAD, erythrocytic δ-aminolevulinic acid dehydratase activity and heme-related parameters on lead workers

劉得佑(Te-Yu Liu)

指導教授 ： 莊弘毅

高雄醫學大學/健康科學院/職業安全衛生研究所/碩士(2007年)

摘要

研究目的
探討鉛作業員工血中鉛濃度以及其他影響ALAD酵素活性因素之相關性。
研究方法
本研究以121名鉛作業員工為主要研究對象，並且以117名非職業性鉛暴露族群作為對照組。針對研究對象蒐集體檢資料，主要包括血中鉛濃度、BMI值、血球比容積、空腹血糖等，並且以問卷調查基本資料、疾病史、抽煙以及飲酒習慣。ALAD酵素活性測定係根據歐洲共同體執行委員會健康保護署的標準化分析流程（European standardized method）進行實驗。ALAD基因多型性分析則是利用聚合脢連鎖反應(PCR)以及限制片段長度多型性分析(RFLP)來判定。
研究結果
研究結果顯示鉛作業員工與對照組血中鉛濃度分別為19.5 μg/Dl（SD = 14.7）與2.9 μg/Dl（SD = 1.9），ALAD酵素活性於鉛作業員工則是顯著低於對照組（42.6 ± 22.4 U/L vs. 64.3 ± 13.8 U/L，P < 0.001）。以總受試對象來看，血中鉛濃度與ALAD酵素活性之間呈現顯著且高度負相關性（P < 0.001），單變項迴歸分析結果ALAD (U/L) = -1.208 PbB + 66.10，相關係數（r）為-0.760。以ALAD酵素活性為依變項，血中鉛濃度、性別、年齡、BMI值、空腹血糖、抽菸以及飲酒的習慣做為自變項，進行線性複迴歸（multiple linear regression）分析，分析結果顯示女性平均ALAD酵素活性顯著比男生低8.15 U/L（P < 0.001）；至於年齡方面，每增加1歲ALAD酵素活性便減少0.16 U/L（P = 0.086）。ALAD酵素活性隨著血鉛濃度的增高而降低，血中鉛濃度每升高1 μg/dL ，ALAD活性便顯著降低1.04 U/L（P < 0.001）。抽菸習慣對於ALAD酵素活性並沒有顯著的影響，但是有飲酒習慣者平均ALAD酵素活性會降低5.31 U/L，達到邊緣顯著意義（P = 0.049）。空腹血糖則是會顯著抑制ALAD酵素活性，平均來說空腹血糖每增加1 mg/dl，ALAD酵素活性便降低0.11 U/L（P < 0.001）。本研究結果顯示在平均血中鉛濃度超過10 μg/dL時，對ALAD酵素活性會有顯著的抑制效應，為可能恕限值。本研究對象238人中帶有ALAD1-1表現型者有229人（96.2％）；帶有ALAD1-2表現型者有8人（3.8％），至於ALAD2-2表現型者沒有在本研究中發現。
結論
本研究結果顯示ALAD酵素活性對於鉛的抑制性有很高的敏感度，且與血中鉛濃度存在明顯的劑量關係，因此ALAD酵素活性可以作為鉛對人體毒性的危害指標。

關鍵字

血中鉛濃度 ； ALAD基因多型性 ； ALAD酵素活性 ； 造血酵素 ； 血液系統

並列摘要

Aims: To investigate the effects of blood lead and other related factors on ALAD activity in lead workers.
Methods: In 121 lead workers and 117 reference subjects, the following data were collected from health examination: blood lead, BMI, glucose AC, and Hct. A questionnaire including of demographic data, medical history, smoking and alcohol consumption was completed by each of subjects. ALAD activity was determined by the standardized method of the European Community. ALAD genotyping was using a method of PCR-RFLP.
Results: Blood lead levels in lead workers and reference subjects were 19.5 μg/dL (SD = 14.7) and 2.9 μg/dL (SD = 1.9), respectively. Lead workers had significantly lower ALAD activity then reference subjects (42.6 ± 22.4 U/L vs. 64.3 ± 13.8 U/L, P < 0.001). To all subjects, the relationship between blood lead and ALAD activity was expressed with ALAD (U/L) = -1.208 PbB + 66.10 (r = -0.760, P < 0.001). According to the multiple regression results, the following independent variables were significant related to ALAD activity. ALAD activity in females were much lower 8.15 U/L then males (P < 0.001). Blood lead and glucose AC were inversely associated with ALAD activity (P < 0.001), but the effect of blood lead was profound. The regression coefficient (BETA) of blood lead and glucose AC were 1.04 and 0.11, respectively. Individuals with alcohol consumption showed lower ALAD activity (P = 0.049). The possible threshold value of blood lead for ALAD activity was determined around 10 μg/dL. In this study, 229 ALAD1-1 homozygotes (96.2%), 8 ALAD1-2 heterozygotes (3.8%) were identified, and none of ALAD2-2 homozygote was observed.
Conclusions: ALAD activity was inhibited by lead sensitively and stoichiometrically, thus ALAD activity may be adopted as a reliable biomarker of lead toxicity in humen.

並列關鍵字

blood lead ； delta-aminolevulinic dehydratase ； prophobilinogen synthesis ； ALAD polymorphism ； ALAD activity ； hemopoietic enzyme ； hematologic system

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