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A Study of the Association between Breastfeeding and DNA Methylation in Peripheral Blood Cells of Infants

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Abstract

This article reports on new data on the association of breastfeeding with DNA methylation in the peripheral blood cells of 37 children aged from 9 months to four years. Whole-genome DNA methylation profiling was performed using the Illumina Methylation EPIC array. The Epigenome-Wide Association Study (EWAS) revealed an association between the duration of breastfeeding and the methylation level of 4276 СpG sites related to 2635 genes. According to the functional annotation, these genes were predominantly involved in the control of cell signaling systems, the development of anatomical structures and cells, and, above all, were related to the development and function of the immune system and the CNS. The results of the study allowed assuming a special role of the oxytocin signaling pathway, as a potential trigger of coordinated epigenetic changes in the genes involved in the CNS function in response to breastfeeding.

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REFERENCES

  1. Victora, C.G., Bahl, R., Barros, A.J., et al., Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect, Lancet Psychiatry, 2016, vol. 387, no. 10017, p. 475—490. https://doi.org/10.1016/S0140-6736(15)01024-7

    Article  Google Scholar 

  2. Mischke, M. and Plösch, T., More than just a gut instinct—the potential interplay between a baby’s nutrition, its gut microbiome, and the epigenome, Am. J. Physiol. Regul. Integr. Comp. Physiol., 2013, vol. 304, no. 12, pp. R1065—R1069. https://doi.org/10.1152/ajpregu.00551.2012

    Article  CAS  PubMed  Google Scholar 

  3. Verduci, E., Banderali, G., Barberi, S., et al., Epigenetic effects of human breast milk, Nutrients, 2014, vol. 6, no. 4, pp. 1711—1724. https://doi.org/10.3390/nu6041711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hartwig, F.P., Loret de Mola, C., Davies N.M., et al., Breastfeeding effects on DNA methylation in the offspring: a systematic literature review, PLoS One, 2017, vol. 12, no. 4. e0175604. https://doi.org/10.1371/journal.pone.0173070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Obermann-Borst, S.A., Eilers, P.H., Tobi, E.W., et al., Duration of breastfeeding and gender are associated with methylation of the LEPTIN gene in very young children, Pediatr. Res., 2013, vol. 74, no. 3, pp. 344—349. https://doi.org/10.1038/pr.2013.95

    Article  CAS  PubMed  Google Scholar 

  6. Tao, M.H., Marian, C., Shields, P.G., et al., Exposures in early life: associations with DNA promoter methylation in breast tumors, J. Dev. Orig. Health Dis., 2013, vol. 4, pp. 182—190. https://doi.org/10.1017/S2040174412000694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Rossnerova, A., Tulupova, E., Tabashidze, N., et al., Factors affecting the 27K DNA methylation pattern in asthmatic and healthy children from locations with various environments, Mutat. Res. 2013, vols. 741–742, pp. 18—26. https://doi.org/10.1017/S2040174412000694

    Article  CAS  PubMed  Google Scholar 

  8. Soto-Ramirez, N., Arshad, S.H., Holloway, J.W., et al., The interaction of genetic variants and DNA methylation of the interleukin-4 receptor gene increase the risk of asthma at age 18 years, Clin. Epigenet., 2013, vol. 5, no. 1, p. 1. https://doi.org/10.1186/1868-7083-5-1

    Article  CAS  Google Scholar 

  9. Simpkin, A.J., Hemani, G., Suderman, M., et al., Prenatal and early life influences on epigenetic age in children: a study of mother—offspring pairs from two cohort studies, Hum. Mol. Genet., 2016, vol. 25, no. 1, pp. 191—201. https://doi.org/10.1093/hmg/ddv456

    Article  CAS  PubMed  Google Scholar 

  10. Kolesnikova, M., Zhukova, M.A., and Ovchinnikova, I., Cognitive development and adaptive skills of children in institutions of Russian Federation, Clin. Psychol. Spec. Educ., 2018, vol. 7, no. 2, pp. 53—69. https://doi.org/10.17759/psyclin.2018070204

    Article  Google Scholar 

  11. Aryee, M.J., Jaffe, A.E., Corrada-Bravo, H., et al., Minfi: a flexible and comprehensive bioconductor package for the analysis of Infinium DNA Methylation microarrays, Bioinformatics, 2014, vol. 30, no. 10, p. 1363—1369. https://doi.org/10.1093/bioinformatics/btu049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Boks, M.P., Derks, E.M., Weisenberger, D.J., et al., The relationship of DNA methylation with age, gender and genotype in twins and healthy controls, PLoS One, 2009, vol. 26, no. 4. e6767. https://doi.org/10.1371/journal.pone.0006767

    Article  CAS  Google Scholar 

  13. Jaffe, A.E. and Irizarry, R.A., Accounting for cellular heterogeneity is critical in epigenome-wide association studies, Genome Biol., 2013, vol. 15, p. R31. https://doi.org/10.1186/gb-2014-15-2-r31

    Article  Google Scholar 

  14. Reinius, L.E., Acevedo, N., Joerink, M., et al., Differential DNA methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility, PLoS One, 2012, vol. 7, no. 7. e41361. https://doi.org/10.1371/journal.pone.0041361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Andersson, Y., Hammarström, M.L., Lönnerdal, B., et al., Formula feeding skews immune cell composition toward adaptive immunity compared to breastfeeding, J. Immunol., 2009, vol. 183, no. 7, pp. 4322—4328. https://doi.org/10.4049/jimmunol.0900829

    Article  CAS  PubMed  Google Scholar 

  16. Casper, J., Zweig, A.S., Villarreal, C., et al., The UCSC genome browser database: 2018 update, Nucleic Acids Res., 2018, vol. 46, no. D1, pp. D762—D769. https://doi.org/10.1093/nar/gkx1020

    Article  CAS  PubMed  Google Scholar 

  17. Harrow, J., Frankish, A., Gonzalez, J.M., et al., GENCODE: the reference human genome annotation for The ENCODE Project, Genome Res., 2012, vol. 22, no. 9, pp. 1760—1764. https://doi.org/10.1101/gr.135350.111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Dennis, G.J., Sherman, B.T., Hosack, D.A., et al., DAVID: Database for Annotation, Visualization, and Integrated Discovery, Genome Biol., 2003, vol. 4, no 5, p. 3.

    Article  Google Scholar 

  19. Chen, E.Y., Tan, C.M., Kou, Y., et al., Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool, BMC Bioinformatics, 2013, vol. 128, no. 14. https://doi.org/10.1186/1471-2105-14-128

  20. Reimand, J., Arak, T., Adler, P., et al., g:Profiler—a web server for functional interpretation of gene lists (2016 update), Nucleic Acids Res., 2016, vol. 44, no. W1, pp. W83—W89. https://doi.org/10.1093/nar/gkw199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Consortium T.G.O., The Gene Ontology project in 2008, Nucleic Acids Res., 2008, vol. 36, database issue, pp. D440–D444. https://doi.org/10.1093/nar/gkm883

  22. Kanehisa, M. and Goto, S., KEGG: Kyoto Encyclopedia of Genes and Genomes, Nucleic Acids Res., 2000, vol. 28, no. 1, pp. 27—30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Thomas, P.D., Campbell, M.J., Kejariwal, A., et al., PANTHER: a library of protein families and subfamilies indexed by function, Genome Res., 2003, vol. 13, no. 9, pp. 2129—2142. https://doi.org/10.1101/gr.772403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Jackson, K.M. and Nazar, A.M., Breastfeeding, the immune response, and long-term health, J. Am. Osteopath. Assoc., 2006, vol. 106, no. 4, pp. 203—207.

    PubMed  Google Scholar 

  25. Uvnäs Moberg, K. and Prime, D.K., Oxytocin effects in mothers and infants during breastfeeding, Infant. 2013, vol. 9, no. 6, pp. 201—206.

    Google Scholar 

  26. Higashida, H., Furuhara, K., Yamauchi, A.M., et al., Intestinal transepithelial permeability of oxytocin into the blood is dependent on the receptor for advanced glycation end products in mice, Sci. Rep., 2017, vol. 7, no. 1, p. 7883. https://doi.org/10.1038/s41598-017-07949-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ludwig, M. and Leng, G., Dendritic peptide release and peptide-dependent behaviours, Nat. Rev. Neurosci., 2006, vol. 7, pp. 126—136. https://doi.org/10.1038/nrn1845

    Article  CAS  PubMed  Google Scholar 

  28. Bakos, J., Srancikova, A., Havranek, T., and Bacova, Z., Molecular mechanisms of oxytocin signaling at the synaptic connection, Neural Plast., 2018, vol. 2018, no. 4864107. https://doi.org/10.1155/2018/4864107

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Funding

The data collection and DNA-methylation analysis were carried out with the support of the Government of the Russian Federation (grant no. 14.Z50.31.0027; PI E.L. Grigorenko); the EWAS was performed with the support of the Russian Foundation for Basic Research (RFBR grant no. 17-06-00667; PI V.V. Odintsova).

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Authors and Affiliations

  1. Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991, Moscow, Russia

    O. Yu. Naumova, S. Yu. Rychkov, Yu. V. Shneider, A. N. Grosheva & O. V. Zhukova

  2. Laboratory of Translational Sciences of Human Development, St. Petersburg State University, 119034, St. Petersburg, Russia

    O. Yu. Naumova, V. V. Odintsova, I. A. Arincina, R. J. Muhamedrahimov & E. L. Grigorenko

  3. Texas Institute for Measurement, Evaluation and Statistics, University of Houston, 77204, Houston, TX, USA

    O. Yu. Naumova & E. L. Grigorenko

  4. Research Center for Obstetrics, Gynecology and Perinatology, 117198, Moscow, Russia

    V. V. Odintsova

Authors
  1. O. Yu. Naumova
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  2. V. V. Odintsova
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  3. I. A. Arincina
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  4. S. Yu. Rychkov
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  5. R. J. Muhamedrahimov
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  6. Yu. V. Shneider
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  7. A. N. Grosheva
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  8. O. V. Zhukova
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  9. E. L. Grigorenko
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Correspondence to O. Yu. Naumova.

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Conflict of interests. The authors declare that they have no conflict of interest.

Statement of compliance with standards of research involving humans as subjects. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from parents of all individual participants involved in the study.

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Naumova, O.Y., Odintsova, V.V., Arincina, I.A. et al. A Study of the Association between Breastfeeding and DNA Methylation in Peripheral Blood Cells of Infants. Russ J Genet 55, 749–755 (2019). https://doi.org/10.1134/S1022795419060103

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