低水平铅暴露儿童的GH/IGF-1轴变化及其与ALAD基因多态性的关系

The changes of axis of GH/IGF1 in children in low level exposure to Lead and its relation to ALAD polymorphism

目的:探讨低水平铅暴露儿童的生长激素/胰岛素样生长因子-1(GH/IGF-1)轴的变化及其与δ-氨基-γ-酮戊酸脱氢酶(ALAD)基因多态性的关系。方法:用钨舟原子吸收光谱法测定来自深圳市区242例学龄前儿童静脉血铅水平(BLL)。按血铅水平将患儿分为两组,A组BLL<50μg/L,B组BLL≥50μg/L。对两组对象的身高(H)、血红蛋白水平(Hb)、ALAD基因、生长激素(GH)、胰岛素样生长因子-1(IGF-1)和胰岛素样生长因子结合蛋白-3(IGFBP-3)水平进行比较。身高测量和血红蛋白检测用常规方法进行;ALAD基因多态性检测采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法;生长激素测定采用化学发光法;IGF-1和IGFBP-3测定采用ELISA法。结果:242例儿童的血铅水平范围为8～146μg/L,几何均数47μg/L。BLL≥50μg/L者占43%,≥100μg/L者占0.8%。两组儿童的IGFBP-3水平差异有统计学意义,B组明显低于A组。身高和IGF-1略有差异,但无统计学意义。基因多态性分析显示,223例为ALAD1-1型,19例为ALAD1-2型,未发现ALAD2-2型。ALAD2基因出现的频率为7.85%。两组儿童突变基因的频率分布差异无统计学意义。结论:本研究发现即使低水平铅暴露也与儿童血IGFBP-3水平明显降低有关,表明铅中毒损害儿童GH/IGF-1轴功能。在低水平铅暴露状态下,ALAD基因的多态性对儿童血铅水平并无明显影响。可能只有在高水平铅暴露时,ALAD基因变异才会对儿童铅中毒易感性发挥作用。

Objective：To explore the effects of low-level exposure to lead on the axis of growth hormone and insulin-like growth factor and correlation of delta-aminolevulinate dehydratase （ALAD） polymorphism to blood lead level in children.Methods：Blood lead level （ BLL） of 242 preschool children were detected by Tungsten Atom absorption spectrum. They were divided into two groups by BLL,group A BLL〈50 μg/L,group B BLL≥50 μg/L.Their height,hemoglobin,ALAD genotype,growth hormone,insulin-like growth factor 1 and insulin-like growth factor binding protein were examined and compared between the two groups.Results：A range of BLL in all subjects was 8~146 μg/L,43% had BLL≥50 μg/L,0.8% had BLL≥100 μg/L.The level of IGFBP3 in group B was lower significantly than that in group A. Height and IGF1 were moderately low in group B ,but no significances. The analysis of ALAD genotype showed that 223 children were ALAD 1-1,19 ALAD 1-2. No ALAD 2-2 type was found. The prevalence of ALAD2 was 7.85%. The frequency of distribution to the two groups was no statistical difference.Conclusion：Low level lead exposure may harm the axis of GH/IGF1 in children.Delta-aminolevulinate dehydratase （ALAD） polymorphism may not relate to BLL of children in low level exposure to lead.