Association Between Birth Weight and DNA Methylation of IGF2, Glucocorticoid Receptor and Repetitive Elements LINE-1 and Alu

Abstract

Aim: We examined the association between birth weight and methylation in the imprinted IGF/H19 loci, the nonimprinted gene NR3C1 and repetitive element DNA (LINE-1 and Alu). Materials & methods: We collected umbilical cord venous blood from 219 infants born in Mexico City (Mexico) as part of a prospective birth cohort study and analyzed DNA methylation using pyrosequencing. Results: Birth weight was not associated with DNA methylation of the regions studied. One of the CpG dinucleotides in the IGF2 imprinting control region (ICR)1 includes a potential C–T SNP. Among individuals with an absence of methylation at this site, probably due to a paternally inherited T allele, birth weight was associated with mean methylation status of both IGF2 ICR1 and ICR2. However, this association would not have survived adjustment for multiple testing. Conclusion: While we did not detect an association between DNA methylation and birth weight, our study suggests a potential gene–epigene interaction between a T allele in the IGF2 ICR1 and methylation of ICRs of IGF2, and fetal growth.

KEYWORDS::

• Alu
• birth weight
• DNA methylation
• fetal growth
• glucocorticoid receptor
• IGF2
• imprinting
• LINE-1
• NR3C1
• SNP

Acknowledgements

The authors would like to thank the cohort participants and staff in Mexico City (Mexico).

Financial & competing interests disclosure

This work was funded by NIH-NIEHS (K23ES022242, R01ES014930, R01ES013744, R01ES020268, P42ES016454, T32ES007069, R01ES000001 and K99ES020346), the Leaves of Grass Foundation and the Klarman Scholars Program at Beth Israel Deaconess Medical Center. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Supplementary data

Additional information

Funding

This work was funded by NIH-NIEHS (K23ES022242, R01ES014930, R01ES013744, R01ES020268, P42ES016454, T32ES007069, R01ES000001 and K99ES020346), the Leaves of Grass Foundation and the Klarman Scholars Program at Beth Israel Deaconess Medical Center. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.