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Associations of LINE-1 DNA Methylation with Preterm Birth in a Prospective Cohort Study.

ABSTRACT: Preterm birth affects over 12% of all infants born in the US yet the biology of early delivery remains unclear, including whether epigenetic mechanisms are involved. We examined associations of maternal and umbilical cord blood long interspersed nuclear element-1 (LINE-1) DNA methylation with length of gestation and odds of preterm birth in singleton pregnancies in Project Viva. In white blood cells from maternal blood during 1(st) trimester (n=914) and 2(nd) trimester (n=922), and from venous cord blood at delivery (n=557), we measured LINE-1 by pyrosequencing (expressed as %5 methyl cytosines within the LINE-1 region analyzed [%5mC]). We ran linear regression models to analyze differences in gestation length, and logistic models for odds of preterm birth (<37 v. ?37 weeks gestation), across quartiles of LINE-1. Mean(SD) LINE-1 levels were 84.3(0.6), 84.5(0.4), and 84.6(0.7) %5mC for 1(st) trimester, 2(nd) trimester and cord blood, respectively. Mean(SD) gestational age was 39.5(1.8) weeks, and 6.5% of infants were born preterm. After adjustment for maternal age, race/ethnicity, BMI, education, smoking status, and fetal sex, women with the highest vs. lowest quartile of 1(st) trimester LINE-1 had longer gestations (0.45 weeks [95% CI 0.12, 0.78]) and lower odds of preterm birth (OR 0.40 [0.17, 0.94]), whereas associations with cord blood LINE-1 were in the opposite direction (-0.45 weeks, -0.83, -0.08) and (OR 4.55 [1.18, 17.5]). In conclusion, higher early pregnancy LINE-1 predicts lower risk of preterm birth. In contrast, preterm birth is associated with lower LINE-1 in cord blood.

SUBMITTER: Burris HH

PROVIDER: S-EPMC3377352 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Associations of LINE-1 DNA Methylation with Preterm Birth in a Prospective Cohort Study.

Burris Heather H HH Rifas-Shiman Sheryl L SL Baccarelli Andrea A Tarantini Letizia L Boeke Caroline E CE Kleinman Ken K Litonjua Augusto A AA Rich-Edwards Janet W JW Gillman Matthew W MW

Journal of developmental origins of health and disease 20120601 3

Preterm birth affects over 12% of all infants born in the US yet the biology of early delivery remains unclear, including whether epigenetic mechanisms are involved. We examined associations of maternal and umbilical cord blood long interspersed nuclear element-1 (LINE-1) DNA methylation with length of gestation and odds of preterm birth in singleton pregnancies in Project Viva. In white blood cells from maternal blood during 1(st) trimester (n=914) and 2(nd) trimester (n=922), and from venous c ...[more]

PMID: 22720130

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Project description:BackgroundPrevious studies have shown that three DNA methylation (DNAm) based algorithms of aging, DNAm PhenoAge acceleration (AgeAccelPheno), DNAm GrimAge acceleration (AgeAccelGrim), and mortality risk score (MRscore), to be strong predictors of mortality and aging related outcomes. We aimed to investigate if and to what extent these algorithms predict cancer.MethodsIn four subsets (n = 727, 1003, 910, and 412) of a population-based cohort from Germany, DNA methylation in whole blood was measured using the Infinium Methylation EPIC BeadChip kit or the Infinium HumanMethylation450K BeadChip Assay (Illumina.Inc, San Diego, CA, USA). AgeAccelPheno, AgeAccelGrim, and a revised MRscore based on 8 CpGs only (MRscore-8CpGs), were calculated. Hazard ratios (HRs) were calculated to assess associations of the three DNAm algorithms with total cancer risk and risk of invasive breast, lung, prostate, and colorectal cancer incidence.FindingsDuring 17 years of follow-up, a total of 697 malignant tumors (thereof breast cancer = 75, lung cancer = 146, prostate cancer = 114, colorectal cancer = 155) were observed. All three algorithms showed strong positive associations with lung cancer risk in a dose response manner, with adjusted HRs per SD increase in AgeAccelPheno, AgeAccelGrim, and MRscore-8CpGs, of 1·37 (1·03-1·82), 1·74 (1·11-2·73), and 2·06 (1·39-3·06), respectively. By contrast, strong inverse associations were seen with breast cancer risk [adjusted HRs 0·65 (0·49-0·86), 0·45 (0·25-0·80), and 0·42 (0·25-0·70), respectively]. Weak positive associations of MRscore-8CpGs were seen with total cancer risk.InterpretationThe DNAm algorithms, particularly the MRscore-8CpGs, have potential to contribute to site-specific cancer risk prediction.FundingThe ESTHER study was funded by grants from the Baden-Württemberg state Ministry of Science, Research and Arts (Stuttgart, Germany), the Federal Ministry of Education and Research (Berlin, Germany), the Federal Ministry of Family Affairs, Senior Citizens, Women and Youth (Berlin, Germany), and the Saarland State Ministry of Health, Social Affairs, Women and the Family (Saarbrücken, Germany). The work of Xiangwei Li was supported by a grant from Fondazione Cariplo (Bando Ricerca Malattie invecchiamento, #2017-0653).

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Dataset Information

Associations of LINE-1 DNA Methylation with Preterm Birth in a Prospective Cohort Study.

Publications

Associations of LINE-1 DNA Methylation with Preterm Birth in a Prospective Cohort Study.

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