Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA.
Neurotoxicology. 2013 Dec;39:65-71. doi: 10.1016/j.neuro.2013.08.002. Epub 2013 Aug 16.
Glutathione-S-transferase gene (GST) polymorphisms can result in variable ability of these enzymes to remove electrophilic substrates. We investigated whether the GSTP1 Val105 and GSTM1 deletion polymorphisms modify the lead-cognitive function association.
We used repeated measures analysis to compare the association between cumulative lead biomarkers-bone lead measured using K-shell X-Ray Fluorescence-and Mini-Mental State Exam (MMSE) score by GST variants, adjusted for covariates, among Normative Aging Study participants, a Boston-based prospective cohort of men. We had complete data for 698 men (providing 1292 observations) for GSTM1 analyses and 595 men (providing 1142 observations) for GSTP1 analyses.
A 15μg/g higher tibia lead concentration (interquartile range of tibia lead) was associated with a 0.24 point decrement in MMSE score among GSTP1 Val105 variant carriers, which was significantly stronger than the association among men with only wild-type alleles (p=0.01). The association among GSTP1 Val105 carriers was comparable to that of 3 years of age in baseline MMSE scores. The association between tibia lead and MMSE score appeared progressively steeper in participants with increasingly more GSTP1 Val105 alleles. A modest association between tibia lead and lower MMSE score was seen among participants with the GSTM1 deletion polymorphism. Neither of the glutathione S-transferase variants was independently associated with cognitive function, nor with lead biomarker measures. The results pertaining to patella lead were similar to those observed for tibia lead.
Our results suggest that the GSTP1 Val105 polymorphism confers excess susceptibility to the cognitive effects of cumulative lead exposure.
谷胱甘肽 S-转移酶基因（GST）多态性可导致这些酶去除亲电底物的能力发生变化。我们研究了 GSTP1 Val105 和 GSTM1 缺失多态性是否会改变铅与认知功能的关联。
我们使用重复测量分析比较了累积铅生物标志物-使用 K 壳 X 射线荧光测量的骨铅-与 GST 变体调整后的 MMSE 评分之间的关联，在基于波士顿的前瞻性队列男性中，正常老化研究参与者。我们有完整的数据进行 GSTM1 分析的 698 名男性（提供 1292 次观察）和 GSTP1 分析的 595 名男性（提供 1142 次观察）。
胫骨铅浓度（胫骨铅的四分位间距）每升高 15μg/g，与 GSTP1 Val105 变体携带者的 MMSE 评分下降 0.24 分相关，这与仅携带野生型等位基因的男性的相关性明显更强（p=0.01）。GSTP1 Val105 携带者的关联与基线 MMSE 评分中 3 年的年龄相当。随着 GSTP1 Val105 携带者中 GSTP1 Val105 等位基因数量的增加，胫骨铅与 MMSE 评分之间的关联变得越来越陡峭。在携带 GSTM1 缺失多态性的参与者中，胫骨铅与较低的 MMSE 评分之间存在适度的关联。两种谷胱甘肽 S-转移酶变体均与认知功能或铅生物标志物测量值无关。与 patella 铅相关的结果与胫骨铅观察到的结果相似。
我们的结果表明，GSTP1 Val105 多态性赋予了对累积铅暴露的认知影响的过度易感性。
