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

Associations of LINE-1 DNA Methylation with Preterm Birth in a Prospective Cohort Study.
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DOI:
10.1017/s2040174412000104
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发表时间:
2012-06
影响因子:
1.7
通讯作者:
Gillman, M. W.
Gillman, M. W.
中科院分区:
医学4区
文献类型:
--
作者:
Burris, H. H.;Rifas-Shiman, S. L.;Baccarelli, A.;Tarantini, L.;Boeke, C. E.;Kleinman, K.;Litonjua, A. A.;Rich-Edwards, J. W.;Gillman, M. W.

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早产影响了美国出生的所有婴儿的12%以上,但早产的生物学仍然不清楚,包括是否涉及表观遗传机制。我们研究了母体和脐带血长散布核元件-1(LINE-1)DNA甲基化与妊娠时间和单胎妊娠早产几率的关系。在妊娠早期(n=914)和妊娠中期(n=922)期间来自母体血液的白细胞以及来自分娩时的静脉脐带血(n=557)的白细胞中,我们通过焦磷酸测序测量LINE-1(表示为分析的LINE-1区域内的%5甲基胞嘧啶[%5mC])。我们运行线性回归模型来分析LINE-1四分位数中妊娠时间的差异,并运行Logistic模型来分析早产几率(<37周与≥37周妊娠)。妊娠早期、妊娠中期和脐带血的平均(SD)LINE-1水平分别为84.3(0.6)、84.5(0.4)和84.6(0.7)% 5 mC。平均(SD)胎龄为39.5(1.8)周,6.5%的婴儿早产。在对母亲年龄、种族/民族、BMI、教育、吸烟状况和胎儿性别进行调整后,妊娠早期LINE-1最高四分位数与最低四分位数的妇女妊娠时间较长(0.45周[95% CI 0.12,0.78])和早产几率较低(OR 0.40 [0.17,0.94]),而与脐带血LINE-1的相关性则相反(-0.45周,-0.83,-0.08)和(OR 4.55 [1.18,17.5])。总之,早期妊娠LINE-1水平越高,早产风险越低。相比之下,早产与脐带血中LINE-1水平较低相关。
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 1st trimester (n=914) and 2nd 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 1st trimester, 2nd 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 1st 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.
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发表时间: 2004-03-01
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发表时间: 2010-11
期刊: Epidemiology (Cambridge, Mass.)
影响因子: --
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