ALAD和VDR基因多态性与铅肾毒性易感性的关系  

Association of Lead Nephrotoxicity with Polymorphism in δ-Aminolevulinic Acid Dehydratase and Vitamin D Receptor Genes

作　　者：杨水莲[1] 叶细标[2] 吴翠娥[2] 鲁翼雯[1] 倪为民[1] 傅华[2] 

机构地区：[1]上海市杨浦区中心医院职业病科,上海200090 [2]复旦大学公共卫生学院,上海200032

出　　处：《环境与职业医学》2002年第6期358-361,共4页Journal of Environmental and Occupational Medicine

摘　　要：[目的 ]探讨δ 氨基乙酰丙酸脱水酶 (ALAD)和维生素D受体 (VDR)基因多态性与铅肾毒性的关系。 [方法 ]选择 2 16名职业铅接触工人。测定血铅 (BPb)、尿铅 (UPb)、尿ALA(UALA)、尿N 乙酰 β D 葡萄糖苷酶 (NAG)活性、尿白蛋白 (ALB)含量和尿肌酐。尿相关指标采用肌酐进行校正。利用限制性片段长度多态 (RFLP)技术进行基因型分析。 [结果 ]铅接触浓度≥ 0 0 3mg/m3 时 ,ALDA 11基因型和ALAD 12基因型工人的平均血铅水平分别是 2 0 6μmol/L和 2 45μmol/L(P >0 0 5 ) ,VDR BB/Bb基因型工人的平均血铅水平 (2 91μmol/L)高于VDR bb基因型工人的平均血铅水平 (2 0μmol/L) ,P <0 0 5。当血铅水平≥ 1 92 μmol/L时 ,ALAD 12基因型工人的NAG活性 (4 5 4U/mmolCr)明显高于ALAD 11基因型工人 (1 2 6U/mmolCr) ,P <0 0 5。ALDA 11基因型工人血铅与NAG活性不呈剂量 效应关系 ,而ALAD 12基因型工人的血铅与NAG活性呈剂量 效应关系 ,回归直线的斜率为 1 5 8(P <0 0 5 )。 [结论 ]本研究提示ALAD和VDR基因多态与血铅水平升高可能有关 ,ALADTo explore the association of lead nephrotoxicity with δ aminolevulinic acid dehydratase and vitamin D receptor gene polymorphism. 216 occupational lead exposed workers were selected. Lead exposure biomarkers:blood lead,urinary lead and δ aminolevulinic acid(ALA) levels were measured. Urinaty N acetyl β glucosaminidase(NAG) activity and albumin concentration were measured as biomarkers of nephrotoxicity and adjusted by creatinine. PCR RFLP method was used for genotyping . When lead exposure concentration was more than or equal to 0 03 mg/m 3,blood lead levels were 2 06 μmol/L in workers with ALAD 11 genotype and 2 45 μmol/L in workers with ALAD 12 genotype;workers with VDR BB/Bb genotype had significantly higher blood lead level than workers with VDR bb genotype had,2 91 μmol/L and 2 0 μmol/L,respectively. For subgroup with blood lead level more than 1 92 μmol/L,workers with ALAD 12 genotype had higher NAG activity than workers with ALAD 11 genotype had,4 54 U/mmol Cr and 1 26 U/mmol Cr respectively, P <0.05.Lead workers with ALAD 12 genotype had larger elevtions in NAG activity with increasing blood lead level compared to lead workers with ALAD 11 genotype.The linear regression coefficients were -0 16( P =0 409) for ALAD 11 group and 1 58( P =0 017)for ALAD 12 group. [Conclusion] ALAD and VDR polymorphism may be related to elevation of blood lead level.ALAD 2 allele may aggravate lead nephrotoxicity.

关 键 词：铅 Δ-氨基乙酰丙酸脱水酶 维生素D受体 基因多态性 肾毒性 

分 类 号：R995[医药卫生—毒理学]