The Usual Suspects- Genetics

This post is part of a 4-part series from Dr. Kim Kutsch on CAMBRA, risk assessment, and the usual suspects that are causing this disease. If you would also like to watch the video, click here.

CAMBRA doesn’t need to be a huge challenge to implement into daily practice. Over the course of sixteen years of clinical work and developing CAMBRA practices into easy to implement tools for dental practices, a powerful thread emerged: Dental caries presents itself in very consistent, identifiable patterns. A caries risk assessment form is a powerful aid, but we can make some diagnosis just from what we see and how it correlates to what we know about this disease. These are the usual suspects.

Genetics has been something of a wildcard in the usual suspects. We know there is a genetic component to caries risk, but the field is still growing and developing. There are a broad array of genes that seem to correlate to caries development and caries risk. We don’t know all of the mechanisms involved in how these genes interact, but we do know they play a role and that our understanding of this area of dental caries disease is still developing.

Of course, dental caries is a pH driven disease. Prolonged low pH environments cause irreversible mineral loss that harms the teeth. When looking at these patterns, it’s with an eye toward treating the low pH conditions that cause so much damage.

The genetic patterns can be more challenging in your practice because there are so few that have been definitively identified as genetic causes for tooth decay. This may change as the field of genetic research grows and can make more specific identifications.

One of the genetic patterns we recognize right now is a [lysel-2 deficiency]. Patients who present with decay only on the mandibular incisors, nowhere else in the mouth, are suffering from this genetic deficiency and have a defective or missing bacteriolytic enzyme that would normally help protect these teeth from a bacterial onslaught. It’s a remarkable pattern, because these patients suffer decay only on those teeth that are generally the safest and longest surviving teeth in the mouth.

A systematic review of all the genes that are known to play a role in dental caries was done in 2014. It found some very logical links–genes linked to tooth development and taste can play a role. More subtle links were found in genes related to white blood cell and enzyme production. Also, genes linked to substances that break down the proteins in the dentin were examined. While some genes seemed like obvious players, there were others that were harder to understand how they would fit into the overall disease picture.

• Individual studies have looked at specific genes with interesting results:
• Beta defensin 1(DEFB1) is a defensive enzyme that helps control bacteria in the mouth. Patients with a particular variant of the gene (G52-A) had 5 times the DMFT scores of others. This study was later replicated in Italy finding corroborating results.
• MMP20 has been shown in studies in Turkey and China to have defensive effects–to reduce the risk of caries. It also showed that the gene in Brazil provided better protection than patients in Turkey, suggesting that other genes are involved in this protective action as well.
• Studies on vitamin D  receptor (VDR) genes have shown that certain variants increase the risk of caries. However, in a study in Czech children, it was not associated with caries, but it was associated with gingivitis.
• A Turkish study found that 88% of decay in the study population could be explained by 3 gene variants and 4 environmental factors alone.
• Not all genes studied appear to play a role in caries. Ficolin-2, associated with several other diseases, did not appear to play any role in dental caries in a study conducted in Poland.
• A variant of the MTRR gene, involved in B12 and homocysteine, was associated with both dental caries and a propensity to be underweight.

It’s important to remember that genes alone don’t cause decay. It takes the correct (or incorrect as the case may be) environment to develop disease. To put if metaphorically, genes may load the gun, but environment pulls the trigger. If you have a patient genetically predisposed to caries, you can’t change their genes, but you can counsel them on how to best control their oral environment to prevent the disease from having a chance to develop.

We see more studies on new genes every month, since this is a growing body of science. We may be able to do genetic testing in the future to help advise our patients on their specific risk of dental caries related to their genetic makeup.