ALAD基因多态性对铅的肾脏毒性易感性作用  

Influence of δ-Aminolevulinic Acid Dehydratase Polymorphismon Lead Renal Toxicity Susceptibility

作　　者：石婷[1] 王永伟[1,2] 杨跃林[1,2] 兰亚佳[1,2] 唐成志[1] 

机构地区：[1]四川大学华西公共卫生学院(华西第四医院)劳动卫生教研室,成都610041 [2]四川大学华西公共卫生学院(华西第四医院)职业卫生应急(重点)实验室

出　　处：《预防医学情报杂志》2014年第5期386-390,共5页Journal of Preventive Medicine Information

摘　　要：目的探讨δ-氨基-γ-酮戊酸脱水酶(ALAD)基因多态性是否对铅肾脏毒性易感性产生影响。方法抽取某钢铁企业的142名男性铅接触炉前工作为研究对象,收集基本信息,采集外周静脉血,检测血铅及相关指标、肾功能指标(血清肌酐、肌酐清除率、血尿素氮、和氨基-乙酰-β-葡萄糖苷酶),同时采用实时定量-聚合酶链反应(RT-PCR)进行ALAD基因型测定,估计累积铅暴露,进行ALAD基因多态性与肾脏损害易感性分析。结果 142名铅接触工人中ALAD1-1基因型有120人(84.51%),ALAD1-2基因型有22人(15.49%),未发现ALAD2-2基因型。等位基因ALAD-1和ALAD-2的频率分别为92.25%和7.75%。ALAD1-2基因型组血铅水平和肌酐清除率分别高于ALAD1-1基因型组的个体,差异有统计学意义(均有P<0.05),ALAD1-2基因型组平均血清肌酐低于ALAD1-1基因型组,差异有统计学意义(P<0.05)。低累积铅暴露时,肌酐清除率随着暴露剂量的增加而升高;但高累积铅暴露时,肌酐清除率随着暴露剂量的增加而下降,而且ALAD1-2基因型个体随着暴露剂量的增加下降更为明显。结论在相同铅暴露情况下,ALAD1-2基因引起血铅升高,进而可能影响血清肌酐和肌酐清除率,而这种作用在累积铅暴露达到一定高的阈值时才显示出来,说明ALAD1-2基因多态性会增加铅慢性肾功能损害的易感性风险。Objective To investigate whether δ-aminolevulinic acid dehydratase（ ALAD） polymorphism can affect the susceptibility of lead renal toxicity. Methods Totally 142 subjects of lead-exposed male workers in the same metal plant were recruited and the essential information and venous blood samples were collected to determine the blood lead and renal function indicators. The ALAD genotyping and susceptibility of renal damage was measured by real time polymerase chain reaction（ RT-PCR） based on accumulated blood lead levels. Results For the genotype of the 142 subjects,120（ 84. 51%） were ALAD1-1; 22（ 15. 49%） were ALAD1-2and none（ 0%） was ALAD2-2.The allele frequency of ALAD-1and ALAD-2were 92. 25% and 7. 75%,respectively. Subjects with ALAD1-2genotype had significantly higher blood lead showed calculated creatinine clearance（ ALE） than those with ALAD1-1 genotype（ P〈0. 05）. Subjects with ALAD1-2genotype had statistically lower average serum creatinine than those with ALAD1-1genotype（ P〈0. 05）. At low ALE stage,the calculated creatinine clearance increased with ALE. However,the calculated creatinine clearance decreased with ALE and the decreasing slope of ALAD1-2was more apparent. Conclusion Exposed to similarly occupational lead,ALAD1-2genotype has higher levels of blood lead concentrations,which may further influence serum creatinine and calculated creatinine clearance at condition of a minimum level of ALE. These results suggest that ALAD genetic polymorphism may affect the susceptibility risk of lead chronic renal dysfunction.

关 键 词：ALAD基因 多态性 肾功能 易感性 高铅暴露 

分 类 号：R135.1[医药卫生—劳动卫生]