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新型δ-氨基-γ-酮戊酸脱水酶(ALAD)基因多态性影响人类对无机铅对神经行为功能影响的易感性的可能性。

Possibilities of newer ALAD polymorphism influencing human susceptibility to effects of inorganic lead on the neurobehavioral functions.

作者信息

Chia Sin-Eng, Huijun Zhou, Theng Tham Mei, Yap Eric

机构信息

Department of Community, Occupational & Family Medicine, National University of Singapore, Singapore, Republic of Singapore.

出版信息

Neurotoxicology. 2007 Mar;28(2):312-7. doi: 10.1016/j.neuro.2006.04.003. Epub 2006 Apr 28.

Abstract

OBJECTIVE

A cross-sectional study was conducted to study the association between some new ALAD polymorphism and susceptibility to effects of inorganic lead on the neurobehavioral functions.

METHOD

We recruited 120 healthy male workers with lead exposure in a factory which manufacture lead stabilizer. The ALAD SNPs studied were HpyCH4, HpyIV RFLP in intron 6, Rsa and Msp RFLP in exon 4, Sau3A in intron 12 and Rsa39488 in exon 5. The World Health Organization Neurobehavioral Core Test Battery (WHO-NCTB) and a few other tests were used. General linear model (GLM) was applied to compare outcome scores between subgroups of each ALAD SNP while controlling for possible confounders.

RESULTS

The mean age of the workers was 39.7 years (S.D. 10.7), mean exposure duration of 10.2 years (S.D. 7.9) and mean blood lead of 22.1 microg/dl (S.D. 9.4). Among the 6 SNPs studied, Rsa and Rsa39488 appear to be the main candidate SNPs. Workers with Rsa and Rsa39488 ALAD 2-2 genotypes fare significantly better in the Aiming Pursue Test Correct (AC), Groove Peg Board non-preferred hand (GPNP), Groove Peg Board Mean (GPM), San Ana Preferred Hand (SAP), San Ana Both Hands (SAB) and AC, GPNH, GPM, Digit Symbol (DIS) tests; respectively compared to Rsa and Rsa39488 ALAD 1-1/1-2 genotypes adjusted for age, race, exposure duration and blood lead levels.

CONCLUSION

The presence of the homozygote Rsa and Rsa39488 ALAD 2-2 seems to offer some protection against the effect of lead on motor dexterity function. While it may appear that newer ALAD polymorphism other than the commonly reported Msp SNP might influence human susceptibility to effects of inorganic lead on the neurobehavioral functions further study involving a larger cohort of workers with Rsa and Rsa39488 ALAD2 allele would be needed to confirm this inference.

摘要

目的

开展一项横断面研究,以探讨某些新的δ-氨基-γ-酮戊酸脱水酶(ALAD)基因多态性与无机铅对神经行为功能影响的易感性之间的关联。

方法

我们招募了一家生产铅稳定剂工厂中120名有铅暴露的健康男性工人。所研究的ALAD单核苷酸多态性(SNP)包括内含子6中的HpyCH4、HpyIV限制性片段长度多态性(RFLP),外显子4中的Rsa和Msp RFLP,内含子第12中的Sau3A以及外显子5中的Rsa39488。使用了世界卫生组织神经行为核心测试组(WHO-NCTB)及其他一些测试。应用一般线性模型(GLM)在控制可能的混杂因素的同时比较各ALAD SNP亚组之间的结果得分。

结果

工人的平均年龄为39.7岁(标准差10.7),平均暴露时长为10.2年(标准差7.9),平均血铅水平为22.1微克/分升(标准差9.4)。在所研究的6个SNP中,Rsa和Rsa39488似乎是主要的候选SNP。与经年龄、种族、暴露时长和血铅水平校正后的Rsa和Rsa39488 ALAD 1-1/1-2基因型相比,具有Rsa和Rsa39488 ALAD 2-2基因型的工人在目标追踪测试正确(AC)、槽式钉板试验非优势手(GPNP)、槽式钉板试验平均值(GPM)、圣安娜试验优势手(SAP)、圣安娜试验双手(SAB)以及AC、GPNH、GPM、数字符号替换试验(DIS)中表现明显更好。

结论

纯合子Rsa和Rsa39488 ALAD 2-2的存在似乎为铅对运动敏捷功能的影响提供了一定保护。虽然除了常见报道的Msp SNP之外,似乎新的ALAD基因多态性可能会影响人类对无机铅对神经行为功能影响的易感性,但需要对更大队列的携带Rsa和Rsa39488 ALAD2等位基因的工人进行进一步研究来证实这一推断。

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