title: GRIN2A polymorphisms and expression levels are associated with lead-induced neurotoxicity.
abstract: 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 lead-induced 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.
authors.affiliation: 1 Wuxi Medical School, Jiangnan University, Wuxi, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wu
authors.affiliation: 2 Department of Occupational Health, Wuxi Center for Disease Control and Prevention, Wuxi, China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 2 Department of Occupational Health, Wuxi Center for Disease Control and Prevention, Wuxi, China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Wang
authors.affiliation: 2 Department of Occupational Health, Wuxi Center for Disease Control and Prevention, Wuxi, China.
authors.forename: Na
authors.initials: N
authors.lastname: Sun
authors.affiliation: 2 Department of Occupational Health, Wuxi Center for Disease Control and Prevention, Wuxi, China.
authors.forename: Chunping
authors.initials: C
authors.lastname: Li
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002681:China; D004785:Environmental Pollutants / Q000633:toxicity; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D057809:HEK293 Cells; D006801:Humans; D007854:Lead / Q000097:blood / Q000633:toxicity*; D020263:Lead Poisoning, Nervous System / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D016273:Occupational Exposure / Q000009:adverse effects; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D004785:Environmental Pollutants; D007854:Lead; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate
keywords: GRIN2A; Lead exposure; case-control; neurotoxicity; polymorphism