期刊
TOXICOLOGY AND INDUSTRIAL HEALTH
卷 33, 期 4, 页码 332-339出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/0748233716647636
关键词
Lead exposure; GRIN2A; neurotoxicity; polymorphism; case-control
资金
- Projects for Medical Scientific Research Foundation, Department of Health, Jiangsu Province [H201246]
- Nature Science Funds of Jiangsu Province [BK20130112]
- Fundamental Research Funds for the Central Universities [JUSRP115A32]
- National Natural Science Foundation of China [81302409]
Lead acts as an antagonist of the N-methyl-D-aspartate receptor (NMDAR). GRIN2A encodes an important subunit of NMDARs and may be a critical factor in the mechanism of lead neurotoxicity. Changes in GRIN2A expression levels or gene variants may be mechanisms of lead-induced neurotoxicity. In this study, we hypothesized that GRIN2A might contribute to lead-induced neurotoxicity. A preliminary HEK293 cell experiment was performed to analyze the association between GRIN2A expression and lead exposure. In addition, in a population-based study, serum GRIN2A levels were measured in both lead-exposed and control populations. To detect further the influence of GRIN2A gene single nucleotide polymorphisms (SNPs) in leadinduced neurotoxicity, 3 tag SNPs (rs2650429, rs6497540, and rs9302415) were genotyped in a case-control study that included 399 lead-exposed subjects and 398 controls. Lead exposure decreased GRIN2A expression levels in HEK293 cells (p < 0.001) compared with lead-free cells. Lead-exposed individuals had lower serum GRIN2A levels compared with controls (p < 0.001), and we found a trend of decreasing GRIN2A level with an increase in blood lead level (p < 0.001). In addition, we found a significant association between rs2650429 CT and TT genotypes and risk of lead poisoning compared with the rs2650429 CC genotype (adjusted odds ratio = 1.42, 95% confidence interval = 1.01-2.00]. Therefore, changes in GRIN2A expression levels and variants may be important mechanisms in the development of lead-induced neurotoxicity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据