Cord blood DNA methylation reflects cord blood C-reactive protein levels but not maternal levels : a longitudinal study and meta-analysis
Yeung, Edwina H. (Eunice Kennedy Shriver National Institute of Child Health and Human Development)
Guan, Weihua (University of Minnesota)
Zeng, Xuehuo (Glotech Inc.)
Salas, Lucas A. (Dartmouth College. Department of Epidemiology)
Mumford, Sunni L. (Eunice Kennedy Shriver National Institute of Child Health and Human Development)
de Prado-Bert, Paula (Institut de Salut Global de Barcelona)
Van Meel, Evelien R. (University Medical Center Rotterdam. Department of Pediatrics)
Malmberg, Anni (University of Helsinki. Department of Psychology and Logopedics)
Sunyer, Jordi (Institut de Salut Global de Barcelona)
Duijts, Liesbeth (University Medical Center Rotterdam. Department of Pediatrics)
Felix, Janine F. (University Medical Center Rotterdam. Department of Pediatrics)
Czamara, Darina (Max-Planck-Institute of Psychiatry. Department of Translational Research in Psychiatry)
Hämäläinen, Esa (University of Eastern Finland)
Binder, Elisabeth B. (Max-Planck-Institute of Psychiatry. Department of Translational Research in Psychiatry)
Raïkkönen, Katri (University of Helsinki. Department of Psychology and Logopedics)
Lahti, Jari (University of Helsinki. Department of Psychology and Logopedics)
London, Stephanie J. (National Institute of Environmental Health Sciences. Department of Health and Human Services)
Silver, Robert M. (University of Utah)
Schisterman, Enrique F. (Eunice Kennedy Shriver National Institute of Child Health and Human Development)

Data:	2020
Resum:	Background: Prenatal inflammation has been proposed as an important mediating factor in several adverse pregnancy outcomes. C-reactive protein (CRP) is an inflammatory cytokine easily measured in blood. It has clinical value due to its reliability as a biomarker for systemic inflammation and can indicate cellular injury and disease severity. Elevated levels of CRP in adulthood are associated with alterations in DNA methylation. However, no studies have prospectively investigated the relationship between maternal CRP levels and newborn DNA methylation measured by microarray in cord blood with reasonable epigenome-wide coverage. Importantly, the timing of inflammation exposure during pregnancy may also result in different effects. Thus, our objective was to evaluate this prospective association of CRP levels measured during multiple periods of pregnancy and in cord blood at delivery which was available in one cohort (i. e. , Effects of Aspirin in Gestation and Reproduction trial), and also to conduct a meta-analysis with available data at one point in pregnancy from three other cohorts from the Pregnancy And Childhood Epigenetics consortium (PACE). Secondarily, the impact of maternal randomization to low dose aspirin prior to pregnancy on methylation was assessed. Results: Maternal CRP levels were not associated with newborn DNA methylation regardless of gestational age of measurement (i. e. , CRP at approximately 8, 20, and 36 weeks among 358 newborns in EAGeR). There also was no association in the meta-analyses (all p > 0. 5) with a larger sample size (n = 1603) from all participating PACE cohorts with available CRP data from first trimester (< 18 weeks gestation). Randomization to aspirin was not associated with DNA methylation. On the other hand, newborn CRP levels were significantly associated with DNA methylation in the EAGeR trial, with 33 CpGs identified (FDR corrected p < 0. 05) when both CRP and methylation were measured at the same time point in cord blood. The top 7 CpGs most strongly associated with CRP resided in inflammation and vascular-related genes. Conclusions: Maternal CRP levels measured during each trimester were not associated with cord blood DNA methylation. Rather, DNA methylation was associated with CRP levels measured in cord blood, particularly in gene regions predominately associated with angiogenic and inflammatory pathways.
Ajuts:	Instituto de Salud Carlos III G03/176 Instituto de Salud Carlos III CB06/02/0041 Ministerio de Sanidad FIS-PI04/1436 Ministerio de Sanidad FIS-PI08/1151 Ministerio de Sanidad FIS-PI11/00610 Ministerio de Sanidad FIS-PI06/0867 Ministerio de Sanidad FIS-PI03/1615 Ministerio de Sanidad MS13/00054 Ministerio de Sanidad CP18/00018 Agència de Gestió d'Ajuts Universitaris i de Recerca 1999/SGR-00241 Fundació la Marató de TV3 090430 European Commission 261357 European Commission 268479 European Commission 633595 European Commission 733206
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	C-reactive protein ; Developmental programming ; DNA methylation ; Inflammation ; Newborn ; Pregnancy
Publicat a:	Clinical Epigenetics, Vol. 12 (April 2020) , art. 60, ISSN 1868-7083

DOI: 10.1186/s13148-020-00852-2
PMID: 32354366

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