Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Avenida do Café s/n - Campus da USP, Ribeirão Preto, SP, 14040-904, Brazil.
Amazonian Education Institute, Rua Maceió 861, Adrianópolis, Manaus, AM, 69057-010, Brazil.
Arch Oral Biol. 2019 Jul;103:12-18. doi: 10.1016/j.archoralbio.2019.05.008. Epub 2019 May 11.
The present cross-sectional, multi-centre, genetic study aimed to determine, whether single nucleotide polymorphisms (SNPs) in tooth agenesis (TA)-associated GLI2 and GLI3 genes contribute to the development of craniofacial skeletal morphology in humans.
Orthodontic patients from an ethnically heterogeneous population were selected for the present study (n = 594). The presence or absence of TA was determined by analysis of panoramic radiography and dental records. The subjects were classified according to their skeletal malocclusion and facial growth pattern by means of digital cephalometric analysis. Genomic DNA was extracted from squamous epithelial cells of the buccal mucosa and SNPs in GLI2 (rs3738880, rs2278741) and GLI3 (rs929387, rs846266) were analysed by polymerase chain reaction using TaqMan chemistry and end-point analysis.
Class II skeletal malocclusion presented a significantly lower frequency of TA (P < 0.05). Subjects without TA showed significantly higher ANB angles (P < 0.05). Genotype and/or allele distributions of the SNPs in GLI2 (rs3738880, rs2278741) and GLI3 (rs846266) were associated with the presence of TA (P < 0.05). The SNPs rs3738880, rs2278741 and rs929387 were also associated with some type of skeletal malocclusion (P < 0.05), but not with the facial growth pattern (P > 0.05). The G allele for TA-related GLI2 rs3738880 was strongly linked to the presence of Class III skeletal malocclusion (OR = 2.03; 95% CI = 1.37-3.03; P<3125 × 10). GLI2 rs2278741 C allele was overrepresented in individuals without TA, suggesting it as a protective factor for this dental phenotype (OR = 0.43; 95% CI = 0.24-0.78; P<625 × 10).
The present study suggests that SNPs in TA-associated GLI2 and GLI3 genes may also play a role in the development of skeletal malocclusions. rs3738880 and rs2278741 in GLI2 seems to contribute to the genetic background for skeletal Class III and TA, respectively. TA could be an additional predictor of craniofacial morphology in some cases. Further research replicating the reported associations should be performed.
本横断面、多中心的遗传研究旨在确定牙缺失（TA）相关 GLI2 和 GLI3 基因中的单核苷酸多态性（SNP）是否有助于人类颅面骨骼形态的发育。
从一个种族多样化的人群中选择正畸患者进行本研究（n=594）。通过全景放射摄影和牙科记录分析确定 TA 的存在或不存在。通过数字头颅测量分析，根据受试者的骨骼错颌和面部生长模式进行分类。从颊黏膜的鳞状上皮细胞中提取基因组 DNA，并通过聚合酶链反应（PCR）使用 TaqMan 化学和终点分析分析 GLI2（rs3738880、rs2278741）和 GLI3（rs929387、rs846266）中的 SNP。
Ⅱ类骨骼错颌畸形的 TA 发生率显著降低（P<0.05）。无 TA 的受试者 ANB 角显著升高（P<0.05）。GLI2（rs3738880、rs2278741）和 GLI3（rs846266）中的 SNP 基因型和/或等位基因分布与 TA 的存在相关（P<0.05）。SNP rs3738880、rs2278741 和 rs929387 也与某些骨骼错颌畸形相关（P<0.05），但与面部生长模式无关（P>0.05）。与 TA 相关的 GLI2 rs3738880 的 G 等位基因与Ⅲ类骨骼错颌畸形的存在密切相关（OR=2.03；95%CI=1.37-3.03；P<3125×10）。GLI2 rs2278741 的 C 等位基因在无 TA 的个体中过度表达，表明其为该牙齿表型的保护因子（OR=0.43；95%CI=0.24-0.78；P<625×10）。
本研究表明，TA 相关 GLI2 和 GLI3 基因中的 SNP 也可能在骨骼错颌畸形的发展中发挥作用。GLI2 中的 rs3738880 和 rs2278741 似乎分别有助于骨骼Ⅲ类和 TA 的遗传背景。在某些情况下，TA 可能是颅面形态的另一个预测因子。应该进行进一步的研究来复制报告的关联。
