Genetic Variants in miRNAs Are Associated With Risk of Non-syndromic Tooth Agenesis.

Min Gu,Fan Yang,Guirong Zhu,Xin Yu,Lan Ma,Lin Wang,Shu Lou,Liwen Fan,Yongchu Pan

doi:10.3389/fphys.2020.01052

Abstract

Non-syndromic tooth agenesis (NSTA) is one of the most common dental abnormalities. MiRNAs participated in the craniofacial and tooth development. Therefore, single nucleotide polymorphisms (SNPs) in miRNA genes may contribute to the susceptibility of non-syndromic tooth agenesis. Here, a total of 625 non-syndromic tooth agenesis cases and 1,144 healthy controls were recruited, and four miRNA SNPs (miR-146a/rs2910164, miR-196a2/rs11614913, pre-miR-605/rs2043556, pre-miR-618/rs2682818) were genotyped by the TaqMan platform. Rs2043556 showed nominal associations with risk of non-syndromic tooth agenesis (PAdd = 0.021) in the overall analysis, as well as upper lateral incisor agenesis (PAdd = 0.047) and lower incisor agenesis (PAdd = 0.049) in the subgroup analysis. Notably, its significant association with upper canine agenesis was observed (PAdd = 0.0016). Rs2043556 affected the mature of miR-605-3p and miR-605-5p while dual-luciferase report analysis indicated that MDM2 was the binding target of miR-605-5p. Our study indicated that pre-miR-605 rs2043556 was associated with risk of non-syndromic tooth agenesis.

Highlights

Tooth agenesis (TA) is one of the most common developmental abnormalities in humans, defined as the absence of one or more permanent teeth, which affects the esthetic, masticatory and occlusal functions of humans
We evaluated the association between nonsyndromic tooth agenesis risk and single nucleotide polymorphisms (SNPs) under additive and allelic models
Single nucleotide polymorphisms in miRNA genes may affect the expression of miRNA and its binding efficiency with target genes, leading to the occurrence of common human diseases (Ryan et al, 2010; Schoen et al, 2017)

Summary

Introduction

Tooth agenesis (TA) is one of the most common developmental abnormalities in humans, defined as the absence of one or more permanent teeth, which affects the esthetic, masticatory and occlusal functions of humans. TA can occur as a syndromic form, which is associated with other genetic diseases, such as non-lethal Raine syndrome (Acevedo et al, 2015), while the more common type is non-syndromic tooth agenesis (NSTA), which occurs as an isolated condition without other birth defects (Fauzi et al, 2018). Previous studies indicated that genomic SNPs were associated with tooth agenesis. (Liu et al, 2013) found an association between rs929387 of GLI3 and non-syndromic tooth agenesis in Chinese Han individuals. Our previous study indicated that rs17563 (Gong et al, 2015), rs15705 and rs317250 (Lu et al, 2016) of BMP4 were associated with non-syndromic tooth agenesis

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