Nonsyndromic Orofacial Clefts in Chile: LINE-1 Methylation and MTHFR Variants

Abstract

Aim: To evaluate the risk of nonsyndromic orofacial clefts (NSOFCs) associated with LINE-1 methylation, as a marker of global DNA methylation, and the effect of MTHFR functional variants on this variable. Patients & methods: LINE-1 methylation was evaluated by bisulfite modification coupled to DNA pyrosequencing in 95 NSOFC cases and 95 controls. In these subjects, MTHFR genotypes for variants c.C677T (rs1801133) and c.A1298C (rs1801131) were obtained. Results: Middle levels (second tertile) of LINE-1 methylation increase the risk of NSOFCs. In addition, LINE-1 methylation depends on c.A1298C genotypes in controls but not in cases. Conclusion: A nonlinear association between global DNA methylation and NSOFCs was detected in this Chilean population, which appears to be influenced by MTHFR functional variants.

Keywords::

• DNA methylation
• LINE-1
• MTHFR
• nonsyndromic orofacial clefts

Acknowledgments

The authors wish to thank the patients, their families and healthy individuals who voluntarily cooperated with us, and the staff members of all cleft children rehabilitation centers, blood banks and University of Chile BioBank.

Financial & competing interests disclosure

This study was supported by the FONDECYT grant 1170805 and by the FONDEQUIP grant EQM-120205. All authors declare 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

For cases and control samples informed written consent was obtained from all subjects or for their parents/legal representatives. The study was approved by the Review Board of the Faculty of Dentistry, Universidad de Chile, following the principles outlined in the Declaration of Helsinki for human investigation.

Additional information

Funding

This study was supported by the FONDECYT grant 1170805 and by the FONDEQUIP grant EQM-120205. All authors declare 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.