Differential gene expression and a functional analysis of PCB-exposed children: Understanding disease and disorder development

Abstract

The goal of the present study is to understand the probable molecular mechanism of toxicities and the associated pathways related to observed pathophysiology in high PCB-exposed populations. We have performed a microarray-based differential gene expression analysis of children (mean age 46.1 months) of Central European descent from Slovak Republic in a well-defined study cohort. The subset of children having high blood PCB concentrations (>75 percentile) were compared against their low PCB counterparts (<25 percentile), with mean lipid-adjusted PCB values of 3.02±1.3 and 0.06±0.03 ng/mg of serum lipid, for the two groups, respectively (18.1±4.4 and 0.3±0.1 ng/ml of serum). The microarray was conducted with the total RNA from the peripheral blood mononuclear cells of the children using an Affymetrix platform (GeneChip Human genome U133 Plus 2.0 Array) and was analyzed by Gene Spring (GX 10.0). A highly significant set of 162 differentially expressed genes between high and low PCB groups (p value <0.00001) were identified and subsequently analyzed using the Ingenuity Pathway Analysis tool. The results indicate that Cell-To-Cell Signaling and Interaction, Cellular Movement, Cell Signaling, Molecular Transport, and Vitamin and Mineral Metabolism were the major molecular and cellular functions associated with the differentially altered gene set in high PCB-exposed children. The differential gene expressions appeared to play a pivotal role in the development of probable diseases and disorders, including cardiovascular disease and cancer, in the PCB-exposed population. The analyses also pointed out possible organ-specific effects, e.g., cardiotoxicity, hepatotoxicity and nephrotoxicity, in high PCB-exposed subjects. A few notable genes, such as BCL2, PON1, and ITGB1, were significantly altered in our study, and the related pathway analysis explained their plausible involvement in the respective disease processes, as mentioned. Our results provided insight into understanding the associated molecular mechanisms of complex gene-environment interactions in a PCB-exposed population. Future endeavors of supervised genotyping of pathway-specific molecular epidemiological studies and population biomarker validations are already underway to reveal individual risk factors in these PCB-exposed populations.

Useful biomarkers for assessing the adverse health effects of PCBs in allergic children: pediatric molecular epidemiology

“…While the above approach has provided a great deal of evidence regarding the deleterious effects of environmental pollution such as those associated with accidental or occupational contamination by lead, arsenic, or mercury (i.e., the effects of pollutants from point sources) [12,13], it has not proved as effective in studies investigating the effects of low concentrations of persistent organic pollutants such as polychlorinated biphenyls (PCBs) and dioxins (i.e., the effects of pollutants from nonpoint sources), which are frequently found among ordinary citizens, although some studies have suggested that exposure to the latter pollutants is associated with the risk of particular diseases [14,15]. This is because the health effects of environmental pollutants represent the end result of complex interactions between toxic chemicals and the physiological condition of vulnerable tissues, which is influenced by both the genetic background of the affected individual and their lifestyle, e.g., their diet and home environment [16,17].…”

Lactational exposure to low levels of the six indicator non-dioxin-like polychlorinated biphenyls induces DNA damage and repression of neuronal activity, in juvenile male mice

“…By contrast, epidemiologic studies have relied on blood or tissue specimens sampled from a lifetime of a high or low exposure to PCBs and their effects on gene expression profiling. As a result, children with high blood PCB concentrations have shown differential gene expression related to cell-to-cell signaling and interactions, cellular movement, cell signaling, molecular transport, and vitamin and mineral metabolism (Dutta et al, 2012). Wens et al (2011) assessed gene expression changes in human peripheral blood mononuclear cells after in vitro incubation with PCB 126 and individual NDL-PCB congeners (PCB 52,138,and 180).…”

Association of PCBs and allergies in children

“…However, some previous studies have detected associations between the risk of various conditions and exposure to such pollutants and the risk [10,11]. The main reason for this is that the health effects of environmental pollutants represent the final consequences of complex interactions between toxic chemicals and the physiological status of the affected tissue, which is influenced by genetic and lifestyle (e.g., the subject's diet and home environment) factors [12,13].…”