DNA methylation levels within the CD14 promoter region are lower in placentas of mothers living on a farm

Authors

  • Gisela G.G. Slaats,

    1. Department of Medicine Solna, Translational Immunology Unit, Karolinska Institutet, Stockholm, Sweden
    2. Department of Nephrology, Graduate School of Regenerative Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
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  • Lovisa E. Reinius,

    1. Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
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  • Johan Alm,

    1. Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset, Sachs' Children's Hospital, Stockholm, Sweden
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  • Juha Kere,

    1. Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
    2. Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden
    3. Department of Medical Genetics, Research Programs Unit, University of Helsinki, and Folkhälsan Institute of Genetics, Helsinki, Finland
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  • Annika Scheynius,

    1. Department of Medicine Solna, Translational Immunology Unit, Karolinska Institutet, Stockholm, Sweden
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  • Maaike Joerink

    Corresponding author
    • Department of Medicine Solna, Translational Immunology Unit, Karolinska Institutet, Stockholm, Sweden
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  • Edited by: Stephan Weidinger

Correspondence

Maaike Joerink, Translational Immunology Unit, Karolinska University Hospital Solna L2:04, SE-171 76 Stockholm, Sweden.

Tel.: 0046-851776697

Fax: 0046-8335724

E-mail: maaike.joerink@ki.se

Abstract

Background

Epigenetic regulation has been suggested to be a link between environmental intrauterine exposures and development of asthma and allergy. The placenta is an essential part of the intrauterine environment. We have previously found the innate immune receptor CD14 to be differentially expressed on the mRNA level in placentas in relation to lifestyle and parental allergen sensitization. We here hypothesized that the promoter region of CD14 may be subject to differential DNA methylation and therefore a link between intrauterine exposure and mRNA expression.

Methods

Ninety-four placentas from the ALADDIN (Assessment of Lifestyle and Allergic Disease During Infancy) study were investigated. We used methylation-sensitive high-resolution melting (MS-HRM) analysis to semi-quantitatively analyze the DNA methylation of the promoter region of CD14 in 36 placentas known to have different CD14 mRNA expression. EpiTYPER was used to validate the MS-HRM data and to analyze an additional 58 placentas selected on mothers living on a farm or not.

Results

MS-HRM analysis on 36 placenta samples revealed a relation between methylation of the CD14 promoter region with the level of CD14 mRNA expression. The MS-HRM and EpiTYPER data correlated highly significantly. EpiTYPER analysis of the additional 58 placentas demonstrated that DNA methylation in the CD14 promoter was significantly lower in placentas of mothers living on a farm compared with mothers not living on a farm.

Conclusion

Our data suggest that epigenetic regulation of CD14 in placenta might be involved in the protective effect of ‘living on a farm’, with regard to allergy development.

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