Further evidence for the role of WNT10A, WNT10B and GREM2 as candidate genes for isolated tooth agenesis

Abstract

Objective: To investigate the association of single nucleotide variants in the candidate genes WNT10A, WNT10B and GREM2 with isolated tooth agenesis.

Setting and sample population: A total of 435 Caucasian individuals (88 cases with isolated tooth agenesis and 347 unrelated controls) were ascertained at the University of Texas Health Science Center at Houston School of Dentistry. Clinical and radiographic examination by orthodontists confirmed the diagnosis of tooth agenesis. Genetic evaluation excluded syndromic forms of tooth agenesis.

Materials and methods: Saliva samples were collected as source of genomic DNA. Fourteen variants in/nearby WNT10A, WNT10B and GREM2 were genotyped to test for association with tooth agenesis. Genotyping was performed using TaqMan chemistry in a real-time polymerase chain reaction assay. Allelic and haplotype frequencies were compared among cases and controls using chi-square tests as implemented in PLINK v.1.06. Bonferroni correction was used and P ≤ 0.004 indicates statistical differences between groups.

Results: Significant associations were found between individual SNPs and SNP combinations in WNT10A, WNT10B and GREM2 SNPs with isolated tooth agenesis (P < 0.004).

Conclusion: Our findings further support a role for variants in WNT10A, WNT10B and GREM2 genes in the aetiology of isolated tooth agenesis. Functional studies are necessary to investigate the biological effects of these gene variants in tooth agenesis phenotypes.

Keywords: GREM2; WNT10A; WNT10B; association; tooth agenesis.