A common variation in EDAR is a genetic determinant of shovel-shaped incisors.

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.

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

Studies on the heredity of dental characteristics in humans have indicated that the variance in many dental traits results from genetic variation. However, the genetic factors that influence commonly occurring dental variants are poorly understood. Paired domain box 9 (PAX9) codes a transcription factor that is important in tooth development. We investigated whether PAX9 polymorphisms are associated with normal variations in tooth agenesis and morphology. The study subjects were 273 Japanese and 223 Korean adults. Single-nucleotide polymorphisms (SNPs) in PAX9 (rs2295222, rs4904155, rs2073244, rs12881240 and rs4904210) were genotyped, and third molar agenesis and mesiodistal and buccolingual diameters were measured. We found that four of the five SNPs were significantly associated with the crown size. However, no SNP was associated with third molar agenesis. In additional analyses on non-metric dental traits, we found significant associations of PAX9 SNPs with shoveling of upper first incisors. In summary, common variants in PAX9 contributed to morphological variation in permanent teeth in humans.

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

Dental morphology is highly diverse among individuals and between human populations. Although it is thought that genetic factors mainly determine common dental variations, only a few such genetic factors have been identified. One study demonstrated that a nonsynonymous single-nucleotide polymorphism (370V/A, rs3827760) in the ectodysplasin A receptor gene (EDAR) is associated with shoveling and double-shoveling grades of upper first incisors and tooth crown size. Here, we examined the association of EDAR 370V/A with several dental characters in Korean and Japanese subjects. A meta-analysis that combined analyses of Korean and Japanese subjects revealed that the Asian-specific 370A allele is associated with an increase in the grades of shoveling and double shoveling, as previously found. We also showed a highly significant association between EDAR 370V/A genotype and crown size, especially mesiodistal diameters of anterior teeth. Moreover, we found that the 370A allele was associated with the presence of hypoconulids of lower second molars. These results indicated that the EDAR polymorphism is responsible, in part, for the Sinodonty and Sundadonty dichotomy in Asian populations, and clearly demonstrated that the EDAR polymorphism has pleiotropic effects on tooth morphology. As the 370A allele is known to be a most likely target of positive selection in Asian populations, some phenotypes associated with the variant may be 'hitchhiking phenotypes', while others may be actual targets of selection.