Non-syndromic tooth agenesis (or non-syndromic congenitally missing tooth) is one of the most common congenital defects in humans affecting the craniofacial function and appearance. Single nucleotide polymorphisms (SNPs) have been associated with an individual’s susceptibility to these anomalies. The aim of the present study was therefore to investigate the roles of the potentially functional SNPs of BMP2 in the occurrence of tooth agenesis. Overall, four potentially functional SNPs of BMP2 (rs15705, rs235768, rs235769 and rs3178250) were selected, and their associations with the susceptibility of tooth agenesis were evaluated in a case-control study of 335 non-syndromic tooth agenesis cases and 444 healthy controls. The SNPs rs15705 and rs3178250 were found to be associated with an individual’s risk of tooth agenesis (P = 0.046 and P = 0.039, respectively). Both SNPs showed an increased risk of mandibular incisor agenesis (rs15705, AA/AC vs. CC = 1.58, 95% CI = [1.06–2.34], P = 0.024; rs3178250, TT/TC vs. CC = 1.60, 95% CI = [1.08–2.37], P = 0.020). Bioinformatics analysis indicated that these two SNPs located at the 3’-untranslated region (3’-UTR) of BMP2 might alter the binding ability of miR-1273d and miR-4639-5p, respectively, which was confirmed by luciferase activity assays in the 293A and COS7 cell lines (P < 0.001 in 293A and P < 0.01 in COS7 for miR-1273d; and P < 0.001 in both cells for miR-4639-5p). Furthermore, BMP2 mRNA expression decreased after transfecting either miR-1273d or miR-4639-5p into these two cell lines (P < 0.01 in 293A and P < 0.001 in COS7 for miR-1273d, and P < 0.01 in both cell lines for miR-4639-5p). Taken together, our findings indicate that rs15705 and rs317250 are associated with the susceptibility of non-syndromic tooth agenesis by possibly affecting miRNAs and mRNA interaction.

Located at 15q22 a susceptibility region for nonsyndromic orofacial clefts (NSOC), TPM1 encodes a group of highly conserved ubiquitous actin-binding proteins involved in the muscle contraction and cytoskeleton organization. Considering the multiple functions of TPM1 gene, we investigated the potential relationship between TPM1 polymorphisms and risk of NSOC in a Chinese Han population. Four tag single nucleotide polymorphisms (tSNPs) of TPM1 (rs11071720, rs3803499, rs12148828, and rs1972041) were selected to conduct a case-control study with 673 NSOC patients and 705 unrelated healthy controls from a Chinese Han population. The SNPs were genotyped by the IPLEX Sequenom MassARRAY platform. SNP rs1972041GA showed a decreased risk of NSOC in heterozygotes (P = 0.038, OR = 0.77, 95%CI = [0.61, 0.99]). Further stratified analysis revealed an enhanced protective effect of the minor allele G at rs197204 on lip with cleft palate (CLP) and cleft lip with or without cleft palate (CL/P) groups under a codominant or dominant model. No association was observed between the remaining three markers (rs11071720, rs3803499, and rs12148828) and NSOC as well as its subgroups. TPM1 polymorphisms might contribute to the etiology of NSOC, and more emphasis should be placed on TPM1 during craniofacial development.

Objective: This study examined the relationships between skeletal deformities and the pharyngeal airway of patients with nonsyndromic unilateral cleft lip and palate (UCLP). Design: Retrospective study. Setting: Orthodontics and Oral and Maxillofacial Surgery Departments in the Affiliated Hospital of Stomatology, Nanjing Medical University, China. Patients, Participants: The sample comprised 30 nonsyndromic UCLP patients and 30 healthy controls. Each group has 23 males and 7 females. Interventions: All cone-beam computed tomography images were obtained with the participant in the standard supine position and asked to bite with intercuspal position without swallowing or moving their heads and tongues during scanning. Main Outcome Measure(s): SNA, SNB, ANB, anterior cranial base, Wits appraisal, maxillary length (PTM-ANS || FH), maxillary position (S-PTM || FH), mandibular length (Go-Pog || MP), FMA, posterior face height, anterior face height, Posterior-Anterior face height, lower face height, pharyngeal airway volumes, and areas were evaluated by Dolphin imaging software. Results: The UCLP group showed significantly decreased SNA, SNB, ANB, PTM-ANS || FH, S-PTM || FH, P-A Face Height compared with the controls. However, the airway volumes and areas showed no significant difference between 2 groups. The total airway volume and minimum cross-sectional area in UCLP patients were related to the Go-Pog || MP and FMA. Conclusions: Patients with UCLP have both the maxillary and mandibular deficiencies in the sagittal dimension. Both the sagittal and vertical relationships of the jaw might affect the airway volume and area. However, no significant difference was detected in airway volume and area in UCLP patients when compared with the controls.