Is Aberrant DNA Methylation a Key Factor in Molar Incisor Hypomineralization?

Abstract

Molar incisor hypomineralization (MIH) is a qualitative disturbance of the enamel of the permanent molars and/or incisors. Its etiology is not clearly defined but is connected with different factors occurring before and after birth. It remains difficult to identify a single factor or group of factors, and the problem is further complicated by various overlapping mechanisms. In this study, we attempted to determine whether DNA methylation—an epigenetic mechanism—plays a key role in the etiology of MIH. We collected the epithelium of the oral mucosa from children with MIH and healthy individuals and analyzed its global DNA methylation level in each child using a 5-mC DNA ELISA kit after DNA isolation. There was no statistically significant difference between the global DNA methylation levels in the study and control groups. Then, we also analyzed the associations of the DNA methylation levels with different prenatal, perinatal, and postnatal factors, using appropriate statistical methods. Factors such as number of pregnancies, number of births, type of delivery, varicella infection (under 3 years old), and high fever (under 3 years old) were significantly important. This work can be seen as the first step towards further studies of the epigenetic background of the MIH etiology.

Epigenetics in developmental defects of enamel: A scoping review

“…The results showed no prominent difference between children with MIH and healthy group. However, significant differences in global DNA methylation levels were connected with five potential factors (number of pregnancies, number of births, type of delivery, varicella infection, and high fever [under 3 years old]) for MIH development (Tynior et al, 2022). Silva MJ et al collected umbilical cord blood from 27 pairs of twins and performed genome‐wide DNA methylation analysis, and examined their oral conditions at the age of 6.…”

“…Only two studies directly explored on samples from human body. Wojciech Tynior et al collected buccal mucosa swabs to test global DNA methylation levels (Tynior et al, 2022). And Silva MJ et al performed genome‐wide DNA methylation analysis collecting umbilical cord blood (Mj et al, 2022).…”

“…Therefore, an examination of relevant genes helps to predict the disease (Smith et al, 2017). Tynior et al performed global DNA methylation examination in children and found that significant differences in global DNA methylation levels were connected with potential factors for MIH development (Tynior et al, 2022). In parallel, dental‐related differentially methylated CpGs and regions were proved to be associated with HSPM (Mj et al, 2022).…”

“…Histone modification, DNA methylation, and non‐coding RNA are the most widely studied epigenetic mechanism in tooth development. A latest study showed that significant differences in global DNA methylation levels were connected with five potential factors for MIH development (Tynior et al, 2022). Hypomineralized Second Primary Molars (HSPM), a type of DDE which can easily turn into early child caries, was proved to have connection with the methylation level of tooth‐development‐related genes at birth (Mj et al, 2022).…”

Enamel Phenotypes: Genetic and Environmental Determinants

“…One twin study, suggesting multiple genes known to be associated with tooth formation, showed differential methylation in children with dental caries and hypomineralized second primary molars [ 107 ]. A study using cheek cells found no difference in global methylation of DNA in children with MH [ 108 ]. While these epigenetic studies are quite preliminary, collectively, they suggest the potential contribution of epigenetics to DDE either as an association, or possibly mechanistically, by altering the expression of genes important to normal enamel development.…”