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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 143-154 |
| Number of pages | 12 |
| Journal | Environment International |
| Volume | 40 |
| Issue number | 1 |
| DOIs | |
| State | Published - Apr 2012 |
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Keywords
- Environmental exposure
- Functional analysis
- Gene expression
- Microarray
- PCB
- PCB-exposed population
ASJC Scopus subject areas
- Environmental Science(all)
Cite this
Differential gene expression and a functional analysis of PCB-exposed children : Understanding disease and disorder development. / Dutta, Sisir K.; Mitra, Partha S.; Ghosh, Somiranjan; Zang, Shizhu; Sonneborn, Dean; Hertz-Picciotto, Irva; Trnovec, Tomas; Palkovicova, Lubica; Sovcikova, Eva; Ghimbovschi, Svetlana; Hoffman, Eric P.
In: Environment International, Vol. 40, No. 1, 04.2012, p. 143-154.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differential gene expression and a functional analysis of PCB-exposed children
T2 - Understanding disease and disorder development
AU - Dutta, Sisir K.
AU - Mitra, Partha S.
AU - Ghosh, Somiranjan
AU - Zang, Shizhu
AU - Sonneborn, Dean
AU - Hertz-Picciotto, Irva
AU - Trnovec, Tomas
AU - Palkovicova, Lubica
AU - Sovcikova, Eva
AU - Ghimbovschi, Svetlana
AU - Hoffman, Eric P.
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
KW - Environmental exposure
KW - Functional analysis
KW - Gene expression
KW - Microarray
KW - PCB
KW - PCB-exposed population
UR - http://www.scopus.com/inward/record.url?scp=84856229233&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856229233&partnerID=8YFLogxK
U2 - 10.1016/j.envint.2011.07.008
DO - 10.1016/j.envint.2011.07.008
M3 - Article
C2 - 21855147
AN - SCOPUS:84856229233
VL - 40
SP - 143
EP - 154
JO - Environmental International
JF - Environmental International
SN - 0160-4120
IS - 1
ER -