A Common Variation in EDAR Is a Genetic Determinant of Shovel-Shaped Incisors

Abstract

Shovel shape of upper incisors is a common characteristic in Asian and Native American populations but is rare or absent in African and European populations. Like other common dental traits, genetic polymorphisms involved in the tooth shoveling have not yet been clarified. In ectodysplasin A receptor (EDAR), where dysfunctional mutations cause hypohidrotic ectodermal dysplasia, there is a nonsynonymous-derived variant, 1540C (rs3827760), that has a geographic distribution similar to that of the tooth shoveling. This allele has been recently reported to be associated with Asian-specific hair thickness. We aimed to clarify whether EDAR 1540C is also associated with dental morphology. For this purpose, we measured crown diameters and tooth-shoveling grades and analyzed the correlations between the dental traits and EDAR genotypes in two Japanese populations, inhabitants around Tokyo and in Sakishima Islands. The number of EDAR 1540C alleles in an individual was strongly correlated with the tooth-shoveling grade (p = 7.7 x 10(-10)). The effect of the allele was additive and explained 18.9% of the total variance in the shoveling grade, which corresponds to about one-fourth of the heritability of the trait reported previously. For data reduction of individual-level metric data, we applied a principal-component analysis, which yielded PC1-4, corresponding to four patterns of tooth size; this result implies that multiple factors are involved in dental morphology. The 1540C allele also significantly affected PC1 (p = 4.9 x 10(-3)), which denotes overall tooth size, and PC2 (p = 2.6 x 10(-3)), which denotes the ratio of mesiodistal diameter to buccolingual diameter.

Effects of an Asian-specific nonsynonymous EDAR variant on multiple dental traits

“…As previously reported, 14 we identified significant effects of EDAR genotype on shoveling, double shoveling, and crown size in the newly examined Japanese subjects (Japanese set 2). The analysis of the Korean subjects also replicated the previous findings on shoveling and double shoveling, but not on crown size.…”

“…14 Here, we confirmed these associations subjecting increased number of Japanese and Korean individuals. In addition, we found that the Asian-specific EDAR variant (370A) was also associated with the presence of hypoconulids of LM2.…”

“…We also used specimens from 73 individuals from the Sakishima Islands, the western islands of Okinawa, that had also participated in previous studies (Japanese set 3). 14,34,35 All the subjects gave informed consent for their participation in this study. This study was conducted with the approval of ethical committees of the Showa University, the Pusan National University and the University of the Ryukyus.…”

“…Kimura et al 14 demonstrated that a nonsynonymous polymorphism in exon 12 of EDAR (370V/A, rs3827760) is associated with shoveling and double shoveling of incisors and crown size of teeth. This polymorphism has also been reported to have an association with morphological variation in human hair.…”

Association of common PAX9 variants with permanent tooth size variation in non-syndromic East Asian populations

“…24 The genetic origins of common dental variations, unlike those of dental anomalies, are poorly understood. While a common nonsynonymous variant in EDAR (Val370Ala) is associated with normal variation in dental traits, such as crown size, shoveling and double shoveling of incisors, 25,26 this EDAR polymorphism alone cannot account for the degree of heritability of such dental traits. Common variations in dental traits are thought to be controlled by multiple factors.…”