Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poznan, Poland.
Clin Genet. 2013 Nov;84(5):429-40. doi: 10.1111/cge.12061. Epub 2012 Dec 7.
Tooth agenesis is one of the most common dental anomalies, with a complex and not yet fully elucidated aetiology. Given the crucial role of the Wnt signalling pathway during tooth development, the purpose of this study was to determine whether nucleotide variants of genes encoding components of this signalling pathway might be associated with hypodontia and oligodontia in the Polish population. A set of 34 single nucleotide polymorphism (SNPs) in 13 WNT and WNT-related genes were analyzed in a group of 157 patients with tooth agenesis and a properly matched control group (n = 430). In addition, direct sequencing was performed to detect mutations in the MSX1, PAX9 and WNT10A genes. Both single-marker and haplotype analyses showed highly significant association between SNPs in the WNT10A gene and the risk for tooth agenesis. Moreover, nine pathogenic mutations within the coding region of the WNT10A gene were identified in 26 out of 42 (62%) tested patients. One novel heterozygous mutation was identified in the PAX9 gene. Borderline association with the risk of non-syndromic tooth agenesis was also observed for the APC, CTNNB1, DVL2 and WNT11 polymorphisms. In conclusion, nucleotide variants of genes encoding important components of the Wnt signalling pathway might influence the risk of tooth agenesis.
牙齿缺失是最常见的牙齿畸形之一，其病因复杂，尚未完全阐明。鉴于 Wnt 信号通路在牙齿发育过程中的关键作用，本研究旨在确定编码该信号通路成分的基因中的核苷酸变异是否可能与波兰人群中的先天性缺牙和少牙有关。在一组 157 名牙齿缺失患者和一组适当匹配的对照组（n=430）中，分析了 13 个 WNT 和 WNT 相关基因中的 34 个单核苷酸多态性（SNP）。此外，还进行了直接测序以检测 MSX1、PAX9 和 WNT10A 基因中的突变。单标记和单倍型分析均显示 WNT10A 基因中的 SNP 与牙齿缺失的风险之间存在高度显著的关联。此外，在 42 名测试患者中的 26 名（62%）中发现了 WNT10A 基因编码区的 9 个致病突变。在 PAX9 基因中还发现了一个新的杂合突变。APC、CTNNB1、DVL2 和 WNT11 多态性与非综合征性牙齿缺失的风险也存在边缘关联。总之，编码 Wnt 信号通路重要成分的基因中的核苷酸变异可能影响牙齿缺失的风险。
