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Spontaneous Preterm Delivery, Dietary Choline Intake and DNA Hypomethylation of Tumor Related Genes in Pregnant Women
Author(s) -
Chen Xinhua,
Bai Guang,
Scholl Theresa O.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.912.2
Subject(s) - gestation , dna methylation , pregnancy , bisulfite , physiology , medicine , confounding , fetus , andrology , biology , gene , obstetrics , genetics , gene expression
Aims Preterm delivery and sub‐optimal fetal growth are associated with each other and affect both mother and infant. Our aims were to determine (1) whether changes in maternal DNA methylation from entry are associated with spontaneous preterm delivery with and without reduced fetal growth and (2) whether dietary nutrient intake including choline and folate are different between preterm cases and term controls. Methods We conducted a case‐control study nested within a large prospective cohort (Camden Study). Gene specific methylation was measured by Methyl‐Profiler PCR Array in a Human Breast Cancer Signature Panel of 24 genes from maternal peripheral leukocytes genomic DNA at entry to care and the 3rd trimester (sampled at 16 and 30 weeks of gestation, respectively). Clonal bisulfite DNA sequencing was performed to confirm the changes in selected genes (CYP1B1, GADD45A and CXCL12). A 24‐hour recall of the previous day's diet was obtained at entry (<20 weeks) and weeks 20 and 28 gestation. The total daily intake of nutrients from all three 24‐hour recalls was averaged for the pregnancy. Multivariable ANOVA with control for confounding was used for data analysis. Results There was significantly increased DNA unmethylation in 15 of 24 genes during the 3rd trimester in cases of spontaneous preterm delivery (n=23) as compared to the controls (n=19) (p<0.05 ‐ p<0.01 for each gene). Similar results were observed by bisulfite sequencing for 3 genes. The change in DNA methylation between late and early gestation was significantly different in cases (overall increase in unmethylation was 4.5 ± 1.4%) compared to the controls (overall decrease in unmethylation was −13.6 ± 2.8%, p<0.0001). A graded pattern of DNA unmethylation was observed in 15 genes. Cases who delivered preterm with reduced fetal growth had the highest level of unmethylation, cases delivering preterm without reduced fetal growth were next and term controls were lowest in unmethylation (p for trend <0.05 to p<0.01 for each gene). Cases of preterm delivery had significantly lower dietary free (p<0.05) and total choline intake (p<0.01) as well as a trend toward lower folate intake (p>0.05). There were no differences in the intake of macronutrients or other B vitamins. Conclusions These data are potentially significant for the identification of women at risk of preterm delivery as well as for the identification of modifiable factors like diet that modulate or influence epigenetic regulation. Support or Funding Information NIH ‐ National Institute of Minority and Health Disparities (1R01MD007828 to XC) and University of Medicine and Dentistry of New Jersey Foundation Grant (PC75‐12 to XC).