Department of Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Department of Endodontics, University of Texas Health Sciences Center at Houston, Houston, Texas, USA.
Caries Res. 2019;53(3):235-241. doi: 10.1159/000492675. Epub 2018 Sep 11.
The purpose of this cohort study was to identify associations between combined oral and bone disease phenotypes and genes present in cell regulatory pathways. The studied pathways play important roles in cellular growth, proliferation, differentiation, and homeostasis. DNA samples extracted from whole saliva of 3,912 individuals were genotyped and these data analyzed according to dental caries experience, periapical lesions, periodontitis, osteoporosis, or temporomandibular joint discomfort. Samples were obtained from the Dental Registry and DNA Repository project at the University of Pittsburgh. Twenty-seven polymorphisms in eight genes related to mTOR or endoplasmic reticulum stress pathways were selected for genotyping. Allele frequencies and Hardy-Weinberg equilibrium were calculated. Analyses were performed comparing genotypes between affected and unaffected individuals for each phenotype, as well as for the associated phenotypes combined. For all analyses, we used the software PLINK with an alpha of 0.002. Borderline associations with multiple variants of several genes were found, suggesting that both pathways may be involved in the susceptibility to multiple conditions affecting the oral cavity and bones. When combining patients that had concomitant dental caries, periodontitis, and periapical pathology, several markers in RHEB showed statistically significant association. Multiple conditions affecting bone and teeth (i.e., dental caries, periodontitis, periapical lesion formation, and osteoporosis) appear to share similar underlying genetic etiological factors, which allow us to hypothesize that instead of individually, they should be studied in conjunction in human populations.
本队列研究旨在确定细胞调节通路中存在的口腔和骨骼疾病表型与基因之间的关联。所研究的通路在细胞生长、增殖、分化和内稳态中发挥着重要作用。从匹兹堡大学的牙科注册处和 DNA 存储库项目中提取了 3912 个人的全唾液 DNA 样本，并根据龋齿经历、根尖病变、牙周炎、骨质疏松症或颞下颌关节不适对这些数据进行了分析。从 27 个与 mTOR 或内质网应激途径相关的基因中选择了 27 个多态性进行基因分型。计算了等位基因频率和 Hardy-Weinberg 平衡。对每个表型以及相关表型进行了比较受影响和未受影响个体之间基因型的分析。对于所有分析，我们使用了软件 PLINK，alpha 值为 0.002。对几个基因的多个变体的边缘关联表明，这两个途径可能都参与了对口腔和骨骼有影响的多种情况的易感性。当将同时患有龋齿、牙周炎和根尖病变的患者结合起来时，RHEB 中的几个标记物显示出统计学上的显著关联。影响骨骼和牙齿的多种疾病（即龋齿、牙周炎、根尖病变形成和骨质疏松症）似乎具有相似的潜在遗传病因因素，这使我们可以假设，它们不应该分别在人类群体中进行研究，而是应该结合在一起进行研究。
