Department of Morphology, São Paulo State University - UNESP, School of Dentistry at Araraquara, Araraquara, Brazil.
School of Dentistry, Group of Basic Dental Science (CBO), CES University, Medellín, Colombia.
Caries Res. 2019;53(2):217-227. doi: 10.1159/000491644. Epub 2018 Aug 21.
Ameloblasts are sensitive cells whose metabolism and function may be affected by inflammatory stimuli. The aim of this study was to evaluate the possible association between polymorphisms in immune response-related genes and molar-incisor hypomineralization (MIH), and their interaction with polymorphisms in amelogenesis-related genes. DNA samples were obtained from 101 nuclear families that had at least 1 MIH-affected child. Eleven single-nucleotide polymorphisms (SNPs) were investigated in immune response genes using TaqMan® technology allele-specific probes. A transmission disequilibrium test was performed to verify overtransmission of alleles in all MIH families, as well as in families only with mild or severe MIH-affected children. Gene-gene interactions between the immune-related and amelogenesis-related polymorphisms were analyzed by determining whether alleles of those genes were transmitted from heterozygous parents more often in association than individually with MIH-affected children. In severe cases of MIH, significant results were observed for rs10733708 (TGFBR1, OR = 3.5, 95% CI = 1.1-10.6). Statistical evidence for gene-gene interactions between rs6654939 (AMELX) and the SNPs rs2070874 (IL4), rs2275913 (IL17A), rs1800872 (IL10), rs1800587 (IL1A), and rs3771300 (STAT1) was observed. The rs2070874 SNP (IL4) was also significantly overtransmitted from heterozygous parents with the rs7526319 (TUFT1) and the rs2355767 (BMP2) SNPs, suggesting a synergistic effect of the transmission of these alleles with susceptibility to MIH. This family-based study demonstrated an association between variation in TGFBR1 and MIH. Moreover, the polymorphisms in immune response and amelogenesis genes may have an additive effect on the risk of developing MIH.
成釉细胞是敏感细胞，其代谢和功能可能受到炎症刺激的影响。本研究旨在评估免疫反应相关基因中的多态性与磨牙-切牙釉质不全（MIH）之间的可能关联，以及它们与成釉相关基因中的多态性的相互作用。从至少有 1 名 MIH 受累子女的 101 个核心家庭中获得 DNA 样本。使用 TaqMan®技术等位基因特异性探针研究了免疫反应基因中的 11 个单核苷酸多态性（SNP）。对所有 MIH 家系以及仅有轻度或重度 MIH 受累子女的家系进行了传递不平衡检验，以验证等位基因的过度传递。通过确定这些基因的等位基因是否更经常从杂合父母传递给 MIH 受累子女，与个体相比，与 MIH 受累子女呈关联，分析了免疫相关和釉质形成相关多态性之间的基因-基因相互作用。在 MIH 的严重病例中，rs10733708（TGFBR1，OR=3.5，95%CI=1.1-10.6）观察到显著结果。rs6654939（AMELX）与 rs2070874（IL4）、rs2275913（IL17A）、rs1800872（IL10）、rs1800587（IL1A）和 rs3771300（STAT1）之间存在基因-基因相互作用的统计证据。rs2070874 SNP（IL4）也从杂合父母中显著过度传递，与 rs7526319（TUFT1）和 rs2355767（BMP2）SNP 一起，提示这些等位基因的传递与 MIH 易感性具有协同作用。这项基于家庭的研究表明，TGFBR1 中的变异与 MIH 之间存在关联。此外，免疫反应和釉质形成基因中的多态性可能对 MIH 发病风险具有附加效应。
