血鉛濃度與HFE基因型對於體內鐵質與紅血球容積之影響

The Effects of Blood lead and HFE Polymorphism on Serum Iron and RBC Mean Corpuscular Volume

林亭儀(Ting-Yi Lin)

指導教授 ： 莊弘毅

高雄醫學大學/健康科學院/公共衛生學研究所/碩士(2008年)

摘要

摘要
研究背景與目的：
鉛會危害人體的健康，長期暴露於高濃度的鉛，其毒性對造血系統造成危害。HFE基因變異與血鐵沈著症有關，而血鐵沈著症則會影響小腸鐵的吸收，造成體內鐵過量。本研究以HFE基因型為修飾因子探討血中鉛濃度影響血清鐵及紅血球之血球容積之情形。
材料與方法:
本研究之研究對象以鉛工廠之作業員工121名為鉛暴露組；非暴露組以非職業性鉛暴露，與鉛作業員工年齡配對之民眾，共117名。資料蒐集針對研究對象之健檢結果，內容包含血中鉛濃度、血球容積比、血清鐵等，同時也以問卷方式調查基本人口學資料、疾病史、抽菸以及飲酒習慣。HFE基因多型性（C282Y, H63D）分析採用聚合酶鏈鎖反應（PCR）以及限制酵素片段長度多型性分析（RFLP）判定。
研究結果：
研究結果顯示鉛作業員工之血鉛濃度為19.75 μg/dL（SD = 14.70），非鉛暴露組之血鉛濃度為2.86 μg/dL（SD = 1.85）；而鉛作業員工之血清鐵濃度為95.65 μg/dL（SD=41.13），非鉛暴露組為94.18 μg/dL（SD=40.86），從單變項分析中結果顯示兩組之血清鐵濃度沒有顯著差異。本研究238名個案之HFE基因型帶有C282Y與 H63D wild-type（CCHH）者有221名（92.9％），帶有H63D異型合子變異者（CCHD）有17名（7.1％），本研究中未發現他種HFE基因型變異。以儲鐵蛋白為依變項，血鉛濃度、HFE基因型、年齡、性別、吸菸習慣、飲酒習慣為自變項進行線性複迴歸分析（multiple linear regression），結果顯示帶有CCHD基因型者較帶有CCHH基因型儲鐵蛋白高122.715 ng/ml，但並未對血清鐵、運鐵蛋白、總鐵結合能以及鐵飽和度造成顯著影響。另外以平均血球容積為依變項，同樣以血鉛濃度、HFE基因型、年齡、性別、吸菸習慣、飲酒習慣為自變項，並加入血鉛濃度與HFE基因型（CCHH/CCHD）相乘之交互作用項進行線性複迴歸分析，分析結果交互作用項呈現統計顯著差異，表示HFE基因型不同，血鉛與平均血球容積之間的關係有所不同。調整干擾因子後，帶有CCHH基因型的人其鉛影響平均血球容積的係數為-0.116(SE=0.045)，而帶有CCHD基因型的係數為0.138(SE=0.124)。
結論：
HFE H63D基因變異（CCHD）改變了鉛對於平均血球容積的影響。故本研究結果發現HFE基因變異對鉛影響平均血球容積有修飾作用。然而鉛對於整個造血系統的影響仍須對其他基因型做進一步研究。
關鍵字：血鉛濃度、HFE基因多型性、紅血球容積、血鐵沉著症

關鍵字

血鉛濃度 ； HFE基因多型性 ； 紅血球容積 ； 血鐵沉著症

並列摘要

Abstract
Background and objective:
Lead is toxic to humans. It is known that exposure to lead for long-term harms the hematopoietic system. HFE mutation is associated with hereditary hemochromatosis that affects the iron absorption in the intestine, and develops iron overload. The objective of this study is to investigate whether the HFE genotype modifies the blood lead levels, affecting distributions of serum iron and the other red blood cell indices.
Material and methods:
121 lead workers and 117 non-exposure age-matched subjects enrolled in the study. We collected the following data from physical examination: blood lead levels, hemoglobin, hematocrit, serum iron, total iron binding caoacity and ferritin. And all subjects filled out questionnaires on the demographic information, medical history, alcohol consumption and smoking history. HFE genotyping for C282Y and H63D was using polymerase chain reaction and restriction fragment length polymorphism (PCR/RFLP).
Results:
The mean blood lead levels in lead workers was 19.75 μg/dL（SD = 14.70）and 2.86 μg/dL（SD = 1.85）for non-exposure subjects. The mean of serum iron in lead workers was 95.65 μg/dL（SD=41.13）,and 94.18 μg/dL（SD=40.86）for non-exposure subjects, which was not significant. Of 238 subjects, 221（92.9％）subjects were wild-type（CCHH） for HFE C282Y and H63D, and 17（7.1％）subjects were heterozygous for H63D mutation（CCHD）. All subjects in this study were free from C282Y mutation. In multiple linear regression analyses that adjusted for blood lead, HFE genotype（C282Y/H63D）, age, gender, smoking and alcohol consumption, serum ferritin for H63D heterozygous mutation was 122.715 ng/ml higher than H63D wild-type （P<0.05）. Using multiple linear regression to analyze the interaction relationship between blood lead and HFE genotype, the HFE genotype would be a modifier for the effect of lead to mean corpuscular volume（MCV）with adjustment of age, gender, smoking, and alcohol consumption. The effects of lead to MCV in the CCHH genotype was -0.116, while the CCHD genotype was 0.138.

Conclusions:
Our research found the significant modifying effect of HFE genotype on the lead affecting MCV. The HFE H63D heterozygous（CCHD）may be a protective factor. However, the toxic effects of lead on hematopoietic system need to study further in the other gene.

Key words: lead, HFE, hemochromatosis, ferritin, mean corpuscular volme

並列關鍵字

lead ； HFE ； hemochromatosis ； ferritin ； mean corpuscular volme

參考文獻

參考文獻

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