Placental promoter methylation of DNA repair genes and prenatal exposure to particulate air pollution: an ENVIRONAGE cohort study Kristof Y Neven, MSc,

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Placental promoter methylation of DNA repair genes and prenatal exposure to particulate air pollution: an ENVIRONAGE cohort study Kristof Y Neven, MSc, Nelly D Saenen, PhD, Letitzia Tarantini, MSc, Bram G Janssen, PhD, Wouter Lefebvre, PhD, Charlotte Vanpoucke, MSc, Prof Valentina Bollati, PhD, Prof Tim S Nawrot, PhD The Lancet Planetary Health Volume 2, Issue 4, Pages e174-e183 (April 2018) DOI: 10.1016/S2542-5196(18)30049-4 Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Terms and Conditions

Figure 1 DNA repair pathways The nucleotide excision repair pathway (A) and the base excision repair pathway (B) are shown, with the most important genes in the pathways indicated. The genes investigated in the present study are highlighted with red boxes. dRP=5' deoxyribose phosphate. PUA= β-unsaturated aldehyde The Lancet Planetary Health 2018 2, e174-e183DOI: (10.1016/S2542-5196(18)30049-4) Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Terms and Conditions

Figure 2 Correlation between placental Alu mutation rate and air pollution exposure Plots show the correlation between Alu mutation rates as absolute percentages and exposure to (A) PM2·5 and (B) black carbon (in μg/m3) during the entire pregnancy. PM2·5=particulate matter with a diameter <2·5 μm. The Lancet Planetary Health 2018 2, e174-e183DOI: (10.1016/S2542-5196(18)30049-4) Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Terms and Conditions

Figure 3 Pollutant exposure and promoter methylation in DNA repair and tumour suppressor genes Effect estimates are presented as the relative change in DNA methylation for an increase of one IQR increment of PM2·5 (3·84 μg/m3) or black carbon (0·36 μg/m3) during the entire pregnancy. Estimates are adjusted for neonates' sex and ethnicity, maternal age, education, smoking habits, and pre-pregnancy body-mass index, and gestational age, batch effect, and season at delivery. *p<0·01. †p<0·0001. The Lancet Planetary Health 2018 2, e174-e183DOI: (10.1016/S2542-5196(18)30049-4) Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Terms and Conditions