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. 2018 Mar 22:10:39.
doi: 10.1186/s13148-018-0472-5. eCollection 2018.

Placental surface area mediates the association between FGFR2 methylation in placenta and full-term low birth weight in girls

Fu-Ying Tian  1 , Xi-Meng Wang  1 , Chuanbo Xie  2 , Bo Zhao  3 , Zhongzheng Niu  4 , Lijun Fan  1 , Marie-France Hivert  5   6   7   8 , Wei-Qing Chen  1   9
Affiliations

Placental surface area mediates the association between FGFR2 methylation in placenta and full-term low birth weight in girls

Fu-Ying Tian et al. Clin Epigenetics. .

Abstract

Background: Fibroblast growth factor receptor 2 (FGFR2) gene encodes a protein of the fibroblast growth factor receptor family. FGFR2 gene expression is associated with the regulation of implantation process of placenta which plays a vital role in fetal growth. DNA methylation is widely known as a mechanism of fetal growth. However, it is unclear whether and how DNA methylation of FGFR2 gene in the placenta is associated with full-term low birth weight. This case-control study aims to explore the links between FGFR2 methylation in placenta and full-term low birth weight and to further examine the mediation effect of placental surface area on this association.

Results: We conducted analyses for each of the five valid CpG sites at FGFR2 in 165 mother-baby pairs (86 FT-LBW vs. 79 FT-NBW) and found that per one standard deviation increase in the DNA methylation of CpG 11 at FGFR2 was associated with 1.64-fold higher risk of full-term low birth weight (OR = 1.64, 95% CI = [1.07, 2.52]) and 0.18 standard deviation decrease in placental surface area (β = - 0.18; standard error = 0.08, p = 0.02). The mediation effect of placental surface area on the association between DNA methylation and full-term low birth weight was significant in girls (OR = 1.38, 95% CI = [1.05, 1.80]) but not in boys. The estimated mediation proportion was 48.38%.

Conclusion: Our findings suggested that placental surface area mediated the association between DNA methylation of FGFR2 in placenta and full-term low birth weight in a sex-specific manner. Our study supported the importance of placental epigenetic changes in placental development and fetal growth.

Keywords: DNA methylation; FGFR2; Low birth weight; Mediation effect; Placental surface area.

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Conflict of interest statement

The Institutional Review Board of the public health school of the Sun Yat-Sen University approved the study, and every single pregnant woman was recruited with informed consent.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Differences of DNA methylation between groups. β value of DNA methylation distribution across CpGs grouped by FT-LBW and FT-NBW (upper panel). Comparison of the association between DNA methylation levels and FT-LBW across CpGs (lower panel)
Fig. 2
Fig. 2
The mediation effects. Girls (a) and boys (b). θ1 is the estimated effect (ln OR) of CpG 11 methylation on FT-LBW adjusting for confounders. θ1’ is the estimated effect (ln OR) of CpG 11 methylation on FT-LBW additionally introducing placental surface area into model. θ2 is the estimated effect (ln OR) of placental surface area on FT-LBW adjusting for confounders. β1 is the coefficient of CpG 11 methylation on placental surface area. Confounders include maternal age, education, family monthly income, ETS exposure during pregnancy, and gestational age. *P value < 0.05; **P value < 0.01
Fig. 3
Fig. 3
The decomposition of effect of the CpG 11 DNA methylation on FT-LBW
See this image and copyright information in PMC

References

    1. WHO. P07 disorders related to short gestation and low birth weight in icd-10. 2016. http://www.icd10data.com/ICD10CM/Codes/P00-P96/P05-P08/P07-/P07.10. Accessed 08/31/2017.
    1. Chen Y, Wu L, Zhang W, Zou L, Li G, Fan L. Delivery modes and pregnancy outcomes of low birth weight infants in China. J Perinatol. 2016;36(1):41–6. 10.1038/jp.2015.137. - PubMed
    1. WHO. Global nutrition targets 2025: low birth weight policy brief. 2014. http://www.who.int/nutrition/publications/globaltargets2025_policybrief_.... Accessed 08/31/2017.
    1. McNamara BJ, Gubhaju L, Chamberlain C, Stanley F, Eades SJ. Early life influences on cardio-metabolic disease risk in aboriginal populations—what is the evidence? A systematic review of longitudinal and case-control studies. Int J Epidemiol. 2012;41(6):1661–1682. doi: 10.1093/ije/dys190. - DOI - PubMed
    1. Pfab T, Slowinski T, Godes M, Halle H, Priem F, Hocher B. Low birth weight, a risk factor for cardiovascular diseases in later life, is already associated with elevated fetal glycosylated hemoglobin at birth. Circulation. 2006;114(16):1687–1692. doi: 10.1161/CIRCULATIONAHA.106.625848. - DOI - PubMed

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