School of Dentistry, Complutense University of Madrid, Madrid, Spain.
BIOCRAN (Craniofacial Biology) Research Group, Complutense University, Madrid, Spain.
Clin Oral Investig. 2021 Apr;25(4):1587-1612. doi: 10.1007/s00784-020-03731-5. Epub 2021 Feb 7.
The present systematic review aims to report and critically assess the findings of the available scientific evidence from genetic association studies examining the genetic variants underlying skeletal class III malocclusion and its sub-phenotypes.
A pre-piloted protocol was registered and followed. The PubMed, Scopus, WOS, Cochrane Library, Gray Open literature, and CADTH databases were explored for genetic association studies following PICOS-based selection criteria. The research was reported in accordance with PRISMA statement and HuGE guidelines. The Q-genie tool was applied to assess the quality of genetic studies. Meta-analysis of genetic association studies was done by means of Meta-Genyo tool.
A total of 8258 articles were retrieved, of which 22 were selected for in-depth analysis. Most of the studies did not differentiate between sub-phenotypes, and the cohorts were heterogeneous regarding ethnicity. Four to five principal components of class III malocclusion explained the phenotypic variation, and gene variants at MYO1H(rs10850110), BMP3(rs1390319), GHR (rs2973015,rs6184, rs2973015), FGF7(rs372127537), FGF10(rs593307), and SNAI3(rs4287555) (p < .05) explained most of the variation across the studies, associated to vertical, horizontal, or combined skeletal discrepancies. Meta-analysis results identified a statistically significant association between risk of class III malocclusion of A allele of the FBN3 rs7351083 [OR 2.13; 95% CI 1.1-4.1; p 0.02; recessive model].
Skeletal class III is a polygenic trait substantially modulated by ethnicity. A multicentric approach should be considered in future studies to increase sample sizes, applying multivariate analysis such as PCA and cluster analysis to characterize existing sub-phenotypes warranting a deeper analysis of genetic variants contributing to skeletal class III craniofacial disharmony.
Grasping the underlying mechanisms of this pathology is critical for a fuller understanding of its etiology, allowing generation of preventive strategies, new individualized therapeutic approaches and more accurate treatment planification strategies.
本系统评价旨在报告和批判性评估现有遗传关联研究中关于骨骼 III 类错[牙合]及其亚表型潜在遗传变异的科学证据。
预先制定了协议并遵循。根据基于 PICOS 的选择标准，在 PubMed、Scopus、WOS、Cochrane 图书馆、灰色开放文献和 CADTH 数据库中探索了遗传关联研究。研究报告符合 PRISMA 声明和 HuGE 指南。应用 Q-genie 工具评估遗传研究的质量。通过 Meta-Genyo 工具对遗传关联研究进行荟萃分析。
共检索到 8258 篇文章，其中 22 篇被选作深入分析。大多数研究没有区分亚表型，且队列在种族方面存在异质性。三到五个 III 类错[牙合]的主要成分解释了表型变异，而 MYO1H(rs10850110)、BMP3(rs1390319)、GHR(rs2973015、rs6184、rs2973015)、FGF7(rs372127537)、FGF10(rs593307)和 SNAI3(rs4287555)的基因变异(rs4287555)（p<.05）解释了大部分研究中的变异，与垂直、水平或综合骨骼差异相关。荟萃分析结果表明，FBN3 rs7351083 的 A 等位基因与 III 类错[牙合]的风险之间存在统计学显著关联[OR 2.13；95%CI 1.1-4.1；p 0.02；隐性模型]。
骨骼 III 类是一种受种族影响很大的多基因特征。未来的研究应考虑采用多中心方法来增加样本量，应用主成分分析（PCA）和聚类分析等多元分析方法来描述现有的亚表型，从而更深入地分析导致骨骼 III 类颅面不协调的遗传变异。
理解这种病理学的潜在机制对于更全面地理解其病因至关重要，这有助于生成预防策略、新的个体化治疗方法和更准确的治疗计划策略。
