Chunping Li

To determine if the rs7079 polymorphism located in the 3′ UTR of the angiotensinogen gene (AGT) altered AGT gene expression and the risk of lead poisoning. A case-control study and luciferase reporter gene assay identified a significant association between rs7079 variants and the risk of lead poisoning. Serum AGT levels were significantly higher in individuals carrying the rs7079 CA genotype, as compared to those carrying the rs7079 CC genotype. The binding of the miRNA mimics miR-31-5p and miR-584-5p to the 3′ UTR of AGT differed based on which rs7079 variant was present, implying that AGT gene expression depends on the rs7079 variant carried. The rs7079 C to A substitution reduced the binding of miR-31-5p/miR-584-5p to the 3′ UTR of AGT, possibly altering the risk of lead poisoning.

Aim: To determine if SNPs located within the 3′-UTR of δ-aminolevulinic acid dehydratase (ALAD) can alter the risk of lead poisoning and the ALAD gene expression. Materials & methods: A case–control study was carried out to find the SNPs in miRNA target region. Luciferase reporter gene assay, qRT-PCR and Western blot was used to determine the relationship between miRNA and SNPs. Results: We found a significant association between rs818708 and the risk of lead poisoning. miR-545–5p was influenced by rs818708 variant and might result in a significant change in ALAD expression. Conclusion: rs818708 T > C can weaken the binding capability between miR-545–5p and 3′-UTR of ALAD and thus may alter the risk of lead poisoning.

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.

Context: GSTP1 is induced by lead, and thus serves as a biomarker of lead exposure. Lead exposure changes DNA methylation status. Objective: We attempted to prove that the methylation of the GSTP1 promoter plays an important role in lead toxicity. Materials and methods: We conducted a case-control study of 53 workers from a battery plant and 53 age and sex matched healthy volunteers to determine whether the methylation level of the GSTP1 promoter is associated with the risk of lead poisoning. We employed methylation-specific PCR (MSP) in cell models to determine the relationship between the GSTP1 methylation level and lead exposure. Results: We found no association between GSTP1 methylation and lead exposure. The difference in methylation frequencies between the exposure group and the controls was not statistically significant (p = 0.401), and individuals with the methylated GSTP1 gene was not associated with the risk of lead poisoning (adjusted OR = 1.36, 95% CI, 0.22–8.24). Conclusion: This study suggests that GSTP1 methylation is not involved in the early phase of lead toxicity. Further studies should be performed to detect the association between GSTP1 methylation and the risk of lead poisoning in later phases.

Context. Occupational and environmental exposures to lead (Pb) are a worldwide concern. DNA methylation plays an important role in the development of Pb toxicity. Here, we try to find out the evidence to prove that the methylation of the LINE-1 promoter may be involved in Pb toxicity. Methods. To determine whether the methylation level of the LINE-1 is associated with the risk of Pb poisoning, we first constructed a Pb acetate-treated cell model to detect the association between LINE-1 methylation and Pb exposure. A case–control study involving 53 workers from a battery plant and 57 healthy volunteers with matching age and gender distribution was carried out. We employed methylation-specific real-time PCR to determine the relationship between LINE-1 methylation level and Pb exposure. Results. In the cell model, Pb exposure significantly decreased the level of LINE-1 methylation (p = 0.009). Significant difference in methylation frequencies was found between the exposed and control samples (p < 0.001). We also found a decreasing trend of LINE-1 methylation level with increasing blood Pb level (p < 0.001). Conclusions. Therefore, the LINE-1 promoter methylation might contribute to the risk of Pb poisoning and identified a possible epigenetic biomarker for Pb toxicity, especially in individuals occupationally exposed to Pb.