AP-HP, Service Odontologie Bretonneau - Louis Mourier HUPNVS and Centre de référence des maladies du métabolisme du phosphore et du calcium, Paris, France.
J Dent Res. 2014 Apr;93(4):360-5. doi: 10.1177/0022034514522060. Epub 2014 Jan 31.
In the literature, the enamelin gene ENAM has been repeatedly designated as a possible candidate for caries susceptibility. Here, we checked whether ENAM variants could increase caries susceptibility. To this aim, we sequenced coding exons and exon-intron boundaries of ENAM in 250 children with a severe caries phenotype and in 149 caries-free patients from 9 French hospital groups. In total, 23 single-nucleotide polymorphisms (SNPs) were found, but none appeared to be responsible for a direct change of ENAM function. Six SNPs had a high minor allele frequency (MAF) and 6 others were identified for the first time. Statistical and evolutionary analyses showed that none of these SNPs was associated with caries susceptibility or caries protection when studied separately and challenged with environmental factors. However, haplotype interaction analysis showed that the presence, in a same variant, of 2 exonic SNPs (rs7671281 and rs3796704; MAF 0.12 and 0.10, respectively), both changing an amino acid in the protein region encoded by exon 10 (p.I648T and p.R763Q, respectively), increased caries susceptibility 2.66-fold independent of the environmental risk factors. These findings support ENAM as a gene candidate for caries susceptibility in the studied population.
在文献中，釉原蛋白基因 ENAM 被反复指定为龋易感性的可能候选基因。在这里，我们检查了 ENAM 变体是否可以增加龋易感性。为此，我们在 250 名具有严重龋表型的儿童和来自 9 个法国医院组的 149 名无龋患者中对 ENAM 的编码外显子和外显子-内含子边界进行了测序。总共发现了 23 个单核苷酸多态性（SNP），但没有一个似乎直接改变了 ENAM 的功能。6 个 SNP 的次要等位基因频率（MAF）较高，另外 6 个 SNP 是首次发现的。统计和进化分析表明，当单独研究并受到环境因素挑战时，这些 SNP 均与龋易感性或龋保护无关。然而，单倍型相互作用分析表明，在同一个变体中存在 2 个外显子 SNP（rs7671281 和 rs3796704；MAF 分别为 0.12 和 0.10），均改变了编码外显子 10 区域的蛋白质中的氨基酸（分别为 p.I648T 和 p.R763Q），独立于环境危险因素，使龋易感性增加了 2.66 倍。这些发现支持 ENAM 作为研究人群中龋易感性的候选基因。
