Sex-Specific Associations between Particulate Matter Exposure and Gene Expression in Independent Discovery and Validation Cohorts of Middle-Aged Men and Women

Karen Vrijens; Ellen Winckelmans; Maria Tsamou; Willy Baeyens; Patrick De Boever; Danyel Jennen; Theo M. de Kok; Elly Den Hond; Wouter Lefebvre; Michelle Plusquin; Hans Reynders; Greet Schoeters; Nicolas Van Larebeke; Charlotte Vanpoucke; Jos Kleinjans; Tim S. Nawrot

doi:10.1289/EHP370

Sex-Specific Associations between Particulate Matter Exposure and Gene Expression in Independent Discovery and Validation Cohorts of Middle-Aged Men and Women

Karen Vrijens, Ellen Winckelmans, Maria Tsamou, Willy Baeyens, Patrick De Boever, Danyel Jennen, Theo M. de Kok, Elly Den Hond, Wouter Lefebvre, Michelle Plusquin, Hans Reynders, Greet Schoeters, Nicolas Van Larebeke, Charlotte Vanpoucke, Jos Kleinjans, Tim S. Nawrot^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: Particulate matter (PM) exposure leads to premature death, mainly due to respiratory and cardiovascular diseases.

Objectives: Identification of transcriptomic biomarkers of air pollution exposure and effect in a healthy adult population.

Methods: Microarray analyses were performed in 98 healthy volunteers (48 men, 50 women). The expression of eight sex-specific candidate biomarker genes (significantly associated with PM10 in the discovery cohort and with a reported link to air pollution-related disease) was measured with qPCR in an independent validation cohort (75 men, 94 women). Pathway analysis was performed using Gene Set Enrichment Analysis. Average daily PM2.5 and PM10 exposures over 2-years were estimated for each participant's residential address using spatiotemporal interpolation in combination with a dispersion model.

Results: Average long-term PM10 was 25.9 (+/-5.4) and 23.7 (+/-2.3) mu g/m(3) in the discovery and validation cohorts, respectively. In discovery analysis, associations between PM10 and the expression of individual genes differed by sex. In the validation cohort, long-term PM10 was associated with the expression of DNAJB5 and EAPP in men and ARHGAP4 (p = 0.053) in women. AKAP6 and LIMK1 were significantly associated with PM10 in women, although associations differed in direction between the discovery and validation cohorts. Expression of the eight candidate genes in the discovery cohort differentiated between validation cohort participants with high versus low PM10 exposure (area under the receiver operating curve = 0.92; 95% CI: 0.85, 1.00; p = 0.0002 in men, 0.86; 95% CI: 0.76, 0.96; p = 0.004 in women).

Conclusions: Expression of the sex-specific candidate genes identified in the discovery population predicted PM10 exposure in an independent cohort of adults from the same area. Confirmation in other populations may further support this as a new approach for exposure assessment, and may contribute to the discovery of molecular mechanisms for PM-induced health effects.

Original language	English
Pages (from-to)	660-669
Number of pages	10
Journal	Environmental Health Perspectives
Volume	125
Issue number	4
DOIs	https://doi.org/10.1289/EHP370
Publication status	Published - Apr 2017

Keywords

LONG-TERM EXPOSURE
HUMAN LUNG-CANCER
AIR-POLLUTION
MALIGNANT PHENOTYPE
PERIPHERAL-BLOOD
EPITHELIAL-CELLS
DNA MICROARRAY
IN-UTERO
LAND-USE
DISEASE

Access to Document

10.1289/EHP370Licence: Other

Cite this

Vrijens, K., Winckelmans, E., Tsamou, M., Baeyens, W., De Boever, P., Jennen, D., de Kok, T. M., Den Hond, E., Lefebvre, W., Plusquin, M., Reynders, H., Schoeters, G., Van Larebeke, N., Vanpoucke, C., Kleinjans, J., & Nawrot, T. S. (2017). Sex-Specific Associations between Particulate Matter Exposure and Gene Expression in Independent Discovery and Validation Cohorts of Middle-Aged Men and Women. Environmental Health Perspectives, 125(4), 660-669. https://doi.org/10.1289/EHP370

@article{880a556ae9ef44f19b090f902bcf8d32,

title = "Sex-Specific Associations between Particulate Matter Exposure and Gene Expression in Independent Discovery and Validation Cohorts of Middle-Aged Men and Women",

abstract = "Background: Particulate matter (PM) exposure leads to premature death, mainly due to respiratory and cardiovascular diseases.Objectives: Identification of transcriptomic biomarkers of air pollution exposure and effect in a healthy adult population.Methods: Microarray analyses were performed in 98 healthy volunteers (48 men, 50 women). The expression of eight sex-specific candidate biomarker genes (significantly associated with PM10 in the discovery cohort and with a reported link to air pollution-related disease) was measured with qPCR in an independent validation cohort (75 men, 94 women). Pathway analysis was performed using Gene Set Enrichment Analysis. Average daily PM2.5 and PM10 exposures over 2-years were estimated for each participant's residential address using spatiotemporal interpolation in combination with a dispersion model.Results: Average long-term PM10 was 25.9 (+/-5.4) and 23.7 (+/-2.3) mu g/m(3) in the discovery and validation cohorts, respectively. In discovery analysis, associations between PM10 and the expression of individual genes differed by sex. In the validation cohort, long-term PM10 was associated with the expression of DNAJB5 and EAPP in men and ARHGAP4 (p = 0.053) in women. AKAP6 and LIMK1 were significantly associated with PM10 in women, although associations differed in direction between the discovery and validation cohorts. Expression of the eight candidate genes in the discovery cohort differentiated between validation cohort participants with high versus low PM10 exposure (area under the receiver operating curve = 0.92; 95% CI: 0.85, 1.00; p = 0.0002 in men, 0.86; 95% CI: 0.76, 0.96; p = 0.004 in women).Conclusions: Expression of the sex-specific candidate genes identified in the discovery population predicted PM10 exposure in an independent cohort of adults from the same area. Confirmation in other populations may further support this as a new approach for exposure assessment, and may contribute to the discovery of molecular mechanisms for PM-induced health effects.",

keywords = "LONG-TERM EXPOSURE, HUMAN LUNG-CANCER, AIR-POLLUTION, MALIGNANT PHENOTYPE, PERIPHERAL-BLOOD, EPITHELIAL-CELLS, DNA MICROARRAY, IN-UTERO, LAND-USE, DISEASE",

author = "Karen Vrijens and Ellen Winckelmans and Maria Tsamou and Willy Baeyens and {De Boever}, Patrick and Danyel Jennen and {de Kok}, {Theo M.} and {Den Hond}, Elly and Wouter Lefebvre and Michelle Plusquin and Hans Reynders and Greet Schoeters and {Van Larebeke}, Nicolas and Charlotte Vanpoucke and Jos Kleinjans and Nawrot, {Tim S.}",

year = "2017",

month = apr,

doi = "10.1289/EHP370",

language = "English",

volume = "125",

pages = "660--669",

journal = "Environmental Health Perspectives",

issn = "0091-6765",

publisher = "U.S. Department of Health and Human Services; National Institute of Environmental Health Sciences",

number = "4",

}

Vrijens, K, Winckelmans, E, Tsamou, M, Baeyens, W, De Boever, P, Jennen, D , de Kok, TM, Den Hond, E, Lefebvre, W, Plusquin, M, Reynders, H, Schoeters, G, Van Larebeke, N, Vanpoucke, C, Kleinjans, J & Nawrot, TS 2017, 'Sex-Specific Associations between Particulate Matter Exposure and Gene Expression in Independent Discovery and Validation Cohorts of Middle-Aged Men and Women', Environmental Health Perspectives, vol. 125, no. 4, pp. 660-669. https://doi.org/10.1289/EHP370

Sex-Specific Associations between Particulate Matter Exposure and Gene Expression in Independent Discovery and Validation Cohorts of Middle-Aged Men and Women. / Vrijens, Karen; Winckelmans, Ellen; Tsamou, Maria et al.
In: Environmental Health Perspectives, Vol. 125, No. 4, 04.2017, p. 660-669.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Sex-Specific Associations between Particulate Matter Exposure and Gene Expression in Independent Discovery and Validation Cohorts of Middle-Aged Men and Women

AU - Vrijens, Karen

AU - Winckelmans, Ellen

AU - Tsamou, Maria

AU - Baeyens, Willy

AU - De Boever, Patrick

AU - Jennen, Danyel

AU - de Kok, Theo M.

AU - Den Hond, Elly

AU - Lefebvre, Wouter

AU - Plusquin, Michelle

AU - Reynders, Hans

AU - Schoeters, Greet

AU - Van Larebeke, Nicolas

AU - Vanpoucke, Charlotte

AU - Kleinjans, Jos

AU - Nawrot, Tim S.

PY - 2017/4

Y1 - 2017/4

N2 - Background: Particulate matter (PM) exposure leads to premature death, mainly due to respiratory and cardiovascular diseases.Objectives: Identification of transcriptomic biomarkers of air pollution exposure and effect in a healthy adult population.Methods: Microarray analyses were performed in 98 healthy volunteers (48 men, 50 women). The expression of eight sex-specific candidate biomarker genes (significantly associated with PM10 in the discovery cohort and with a reported link to air pollution-related disease) was measured with qPCR in an independent validation cohort (75 men, 94 women). Pathway analysis was performed using Gene Set Enrichment Analysis. Average daily PM2.5 and PM10 exposures over 2-years were estimated for each participant's residential address using spatiotemporal interpolation in combination with a dispersion model.Results: Average long-term PM10 was 25.9 (+/-5.4) and 23.7 (+/-2.3) mu g/m(3) in the discovery and validation cohorts, respectively. In discovery analysis, associations between PM10 and the expression of individual genes differed by sex. In the validation cohort, long-term PM10 was associated with the expression of DNAJB5 and EAPP in men and ARHGAP4 (p = 0.053) in women. AKAP6 and LIMK1 were significantly associated with PM10 in women, although associations differed in direction between the discovery and validation cohorts. Expression of the eight candidate genes in the discovery cohort differentiated between validation cohort participants with high versus low PM10 exposure (area under the receiver operating curve = 0.92; 95% CI: 0.85, 1.00; p = 0.0002 in men, 0.86; 95% CI: 0.76, 0.96; p = 0.004 in women).Conclusions: Expression of the sex-specific candidate genes identified in the discovery population predicted PM10 exposure in an independent cohort of adults from the same area. Confirmation in other populations may further support this as a new approach for exposure assessment, and may contribute to the discovery of molecular mechanisms for PM-induced health effects.

AB - Background: Particulate matter (PM) exposure leads to premature death, mainly due to respiratory and cardiovascular diseases.Objectives: Identification of transcriptomic biomarkers of air pollution exposure and effect in a healthy adult population.Methods: Microarray analyses were performed in 98 healthy volunteers (48 men, 50 women). The expression of eight sex-specific candidate biomarker genes (significantly associated with PM10 in the discovery cohort and with a reported link to air pollution-related disease) was measured with qPCR in an independent validation cohort (75 men, 94 women). Pathway analysis was performed using Gene Set Enrichment Analysis. Average daily PM2.5 and PM10 exposures over 2-years were estimated for each participant's residential address using spatiotemporal interpolation in combination with a dispersion model.Results: Average long-term PM10 was 25.9 (+/-5.4) and 23.7 (+/-2.3) mu g/m(3) in the discovery and validation cohorts, respectively. In discovery analysis, associations between PM10 and the expression of individual genes differed by sex. In the validation cohort, long-term PM10 was associated with the expression of DNAJB5 and EAPP in men and ARHGAP4 (p = 0.053) in women. AKAP6 and LIMK1 were significantly associated with PM10 in women, although associations differed in direction between the discovery and validation cohorts. Expression of the eight candidate genes in the discovery cohort differentiated between validation cohort participants with high versus low PM10 exposure (area under the receiver operating curve = 0.92; 95% CI: 0.85, 1.00; p = 0.0002 in men, 0.86; 95% CI: 0.76, 0.96; p = 0.004 in women).Conclusions: Expression of the sex-specific candidate genes identified in the discovery population predicted PM10 exposure in an independent cohort of adults from the same area. Confirmation in other populations may further support this as a new approach for exposure assessment, and may contribute to the discovery of molecular mechanisms for PM-induced health effects.

KW - LONG-TERM EXPOSURE

KW - HUMAN LUNG-CANCER

KW - AIR-POLLUTION

KW - MALIGNANT PHENOTYPE

KW - PERIPHERAL-BLOOD

KW - EPITHELIAL-CELLS

KW - DNA MICROARRAY

KW - IN-UTERO

KW - LAND-USE

KW - DISEASE

U2 - 10.1289/EHP370

DO - 10.1289/EHP370

M3 - Article

C2 - 27740511

SN - 0091-6765

VL - 125

SP - 660

EP - 669

JO - Environmental Health Perspectives

JF - Environmental Health Perspectives

IS - 4

ER -