GREM2 nucleotide variants and the risk of tooth agenesis

• Published in: Oral diseases 2018-05, Vol.24 (4), p.591-599
• Main Authors: Mostowska, A, Biedziak, B, Zadurska, M, Bogdanowicz, A, Olszewska, A, Cieślińska, K, Firlej, E, Jagodziński, PP
• Format: Article
• Language: English
• Subjects: Alleles; bone morphogenetic protein antagonist; Bone morphogenetic proteins; Dentistry; Etiology; Gene frequency; GREM2; Mutation; Oral diseases; Phenotypes; Teeth; tooth agenesis
• ISSN: 1354-523X; 1601-0825
• DOI: 10.1111/odi.12793

Objective The etiology of tooth agenesis (TA) is multifactorial and still not fully understood. The aim of the study was to test whether variants of GREM2, encoding a bone morphogenetic protein (BMP) antagonist, are associated with the risk of this common dental anomaly in a Polish population. Subjects and Methods Direct sequencing of the GREM2 coding sequence including exon/intron boundaries was performed in 95 patients with both hypodontia and oligodontia. All identified GREM2 variants were then further tested in an independent group of patients (n = 163) and controls (n = 184). Results The previously described, functional GREM2 mutation (c.226C > G, p.Gln76Glu) was identified in two patients with hypodontia and associated dental anomalies, including taurodontism and microdontia. This mutation generating an allele with increased inhibitory activity was not detected in the control group. The second identified GREM2 variant, c.‐1‐21C > T (rs11806449), was not associated with the risk TA. The polymorphism allele frequency in both patients and controls was 0.21 (OR = 1.0, 95%CI: 0.76–1.46). The rs11806449 did not correlate either with the overall TA phenotype or hypodontia/oligodontia phenotypes. Conclusion Our study confirmed that GREM2 is a candidate gene for tooth agenesis, which mutations can explain, however, only a small fraction of the genetic contribution to the pathogenesis of this anomaly.