Common variants of EDA are associated with non-syndromic hypodontia

Objective: The aim of this case-control study was to investigate the association between non-syndromic hypodontia and nineteen common variants of candidate genes ectodysplasin A (EDA), paired box 9 (PAX9), msh homeobox 1 (MSX1) and axis inhibition protein 2 (AXIN2).

Settings and sample population: Sixty-one hypodontia cases were frequency-matched to 253 controls with no missing teeth (excluding the third molars).

Material and methods: Self-report data and DNA samples were collected from each participant.

Results: The sample had a mean age of 16.6 years (SD = 7.3), with most participants being female (59.6%), and of New Zealand European origin (75.4%). Using multiple logistic regression analysis, it was found that the T-allele of rs12853659 (EDA) and the G-allele of rs2428151 (EDA) were both associated with a higher risk of hypodontia (odds ratio, OR = 2.79, 95% CI = 1.11-7.01; and OR = 2.87, 95% CI = 1.04-7.94, respectively). The G-allele of rs2520378 (EDA) showed a protective effect with an OR of 0.61 (95% CI = 0.38-0.99). The EDA SNP findings were consistent with previous reports included in a meta-analysis. No associations were found with the PAX9, AXIN2 and MSX1 genes, after adjusting for sex and ethnicity.

Conclusions: Common variants of the EDA genes are associated with specific phenotypes of non-syndromic hypodontia, thus confirming their role in the regulatory pathways of normal tooth development. However, larger samples are needed to investigate the association further.