Association between length of gestation and cervical DNA methylation of PTGER2 and LINE 1-HS.
Worldwide, more than 1 in 10 infants is born prior to 37 weeks gestation. Preterm birth can lead to increased mortality risk and poor life-long health and neurodevelopmental outcomes. Whether environmental risk factors affect preterm birth through epigenetic phenomena is largely unstudied. We sought to determine whether preterm risk factors, such as smoke exposure and education, were associated with cervical DNA methylation in the prostaglandin E receptor 2 gene (PTGER2) and a repetitive element, long interspersed nuclear element-1 Homo sapiens-specific (LINE 1-HS). Second, we aimed to determine whether mid-pregnancy DNA methylation of these regions in cervical samples could predict the length of gestation. We obtained a cervical swab between 16-19 weeks gestation from 80 women participating in a Mexico City birth cohort, used pyrosequencing to analyze DNA methylation of PTGER2 and LINE 1-HS, and examined associations with maternal covariates. We used accelerated failure time models to analyze associations of DNA methylation with the length of gestation. DNA methylation of both sequences was associated with Pap smear inflammation. LINE 1-HS methylation was associated with smoke exposure, BMI and parity. In adjusted models, gestations were 3.3 days longer (95%CI 0.6, 6.0) for each interquartile range of PTGER2 DNA methylation. Higher LINE 1-HS methylation was associated with shorter gestations (-3.3 days, 95%CI -6.5, -0.2). In conclusion, cervical DNA methylation was associated with risk factors for preterm birth and the length of gestation.
Department of Neonatology; Beth Israel Deaconess Medical Center and Division of Newborn Medicine; Boston Children's Hospital and Harvard Medical School; Boston, MA USA.
Heather H
HH
Burris
Laboratory of Environmental Epigenetics; Exposure Epidemiology and Risk Program; Harvard School of Public Health; Boston, MA USA; Department of Environmental Health; Harvard School of Public Health; Boston, MA USA.
Andrea A
AA
Baccarelli
Laboratory of Environmental Epigenetics; Exposure Epidemiology and Risk Program; Harvard School of Public Health; Boston, MA USA; Department of Clinical Sciences and Community Health; University of Milan, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico; Milan, Italy.
Valeria
V
Motta
Laboratory of Environmental Epigenetics; Exposure Epidemiology and Risk Program; Harvard School of Public Health; Boston, MA USA; Department of Environmental Health; Harvard School of Public Health; Boston, MA USA.
Hyang-Min
HM
Byun
Department of Environmental Health; Harvard School of Public Health; Boston, MA USA.
Allan C
AC
Just
Center for Evaluation Research and Surveys; National Institute of Public Health; Cuernavaca, Mexico.
Adriana
A
Mercado-Garcia
Department of Environmental Health; Harvard School of Public Health; Boston, MA USA.
Joel
J
Schwartz
Department of Pediatrics and Preventative Medicine; Icahn School of Medicine at Mount Sinai; New York, NY USA.
Katherine
K
Svensson
Center for Evaluation Research and Surveys; National Institute of Public Health; Cuernavaca, Mexico.
Martha M
MM
Téllez-Rojo
Department of Pediatrics and Preventative Medicine; Icahn School of Medicine at Mount Sinai; New York, NY USA.
Robert O
RO
Wright
D000328:Adult; D002584:Cervix Uteri / Q000378:metabolism*; D015331:Cohort Studies; D019175:DNA Methylation; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D011247:Pregnancy / Q000502:physiology*; D047928:Premature Birth / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D055815:Young Adult
C545644:PTGER2 protein, human; D058307:Receptors, Prostaglandin E, EP2 Subtype
Cervix; DNA methylation; LINE 1; PTGER2; Preterm birth; epigenetics