The human EDAR 370V/A polymorphism affects tooth root morphology potentially through the modification of a reaction–diffusion system

Abstract

Morphological variations in human teeth have long been recognized and, in particular, the spatial and temporal distribution of two patterns of dental features in Asia, i.e., Sinodonty and Sundadonty, have contributed to our understanding of the human migration history. However, the molecular mechanisms underlying such dental variations have not yet been completely elucidated. Recent studies have clarified that a nonsynonymous variant in the ectodysplasin A receptor gene (EDAR 370V/A; rs3827760) contributes to crown traits related to Sinodonty. In this study, we examined the association between the EDAR polymorphism and tooth root traits by using computed tomography images and identified that the effects of the EDAR variant on the number and shape of roots differed depending on the tooth type. In addition, to better understand tooth root morphogenesis, a computational analysis for patterns of tooth roots was performed, assuming a reaction–diffusion system. The computational study suggested that the complicated effects of the EDAR polymorphism could be explained when it is considered that EDAR modifies the syntheses of multiple related molecules working in the reaction–diffusion dynamics. In this study, we shed light on the molecular mechanisms of tooth root morphogenesis, which are less understood in comparison to those of tooth crown morphogenesis.

Molecular basis and genetics of hypohidrotic ectodermal dysplasias

“…The V370A variant is a conservative amino acid substitu tion in the EDAR gene identified in Asian and Latin American populations by whole genome sequencing (Park et al, 2012). It is believed to be a gain-of-function mutation that leads to a 2-fold increase in the activation of the NF-κB pathway (Kataoka et al, 2021) and, accordingly, correlates with increased hair thickness and special tooth morphology in representatives of Asia and indigenous peoples of the USA (Bryk et al, 2008). An interesting fact is that this variant was selected, presumably in Central China, about 30,000 years ago, and the presence in the genotype of pathogenic variants in the EDA gene in the presence of V370A reduces the severity of clinical manifestations of anhidrotic ectodermal dysplasia (Cluzeau et al, 2011).…”