Alexandra Dehesa-Santos1, Paula Iber-Diaz1, Alejandro Iglesias-Linares2,3,4. 1. School of Dentistry, Complutense University of Madrid, Madrid, Spain. 2. School of Dentistry, Complutense University of Madrid, Madrid, Spain. aleigl01@ucm.es. 3. BIOCRAN (Craniofacial Biology) Research Group, Complutense University, Madrid, Spain. aleigl01@ucm.es. 4. Complutense University of Madrid, Madrid, Spain. aleigl01@ucm.es.
Abstract
OBJECTIVES: 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. MATERIAL AND METHODS: 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. RESULTS: 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]. CONCLUSION: 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. CLINICAL RELEVANCE: 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.
OBJECTIVES: 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. MATERIAL AND METHODS: 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. RESULTS: 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 FBN3rs7351083 [OR 2.13; 95% CI 1.1-4.1; p 0.02; recessive model]. CONCLUSION: 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. CLINICAL RELEVANCE: 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.
Entities:
Keywords:
Genetic factors; Malocclusion sub-phenotypes; Principal component analysis; Skeletal class III malocclusion
Authors: Ricardo Machado Cruz; Henrique Krieger; Ricardo Ferreira; James Mah; James Hartsfield; Silviene Oliveira Journal: Am J Med Genet A Date: 2008-01-01 Impact factor: 2.802
Authors: T Nikopensius; M Saag; T Jagomägi; T Annilo; M Kals; P A Kivistik; L Milani; A Metspalu Journal: J Dent Res Date: 2013-08-21 Impact factor: 6.116
Authors: C S G da Fontoura; S F Miller; G L Wehby; B A Amendt; N E Holton; T E Southard; V Allareddy; L M Moreno Uribe Journal: J Dent Res Date: 2015-04-24 Impact factor: 6.116
Authors: Peter Claes; Jasmien Roosenboom; Julie D White; Tomek Swigut; Dzemila Sero; Jiarui Li; Myoung Keun Lee; Arslan Zaidi; Brooke C Mattern; Corey Liebowitz; Laurel Pearson; Tomás González; Elizabeth J Leslie; Jenna C Carlson; Ekaterina Orlova; Paul Suetens; Dirk Vandermeulen; Eleanor Feingold; Mary L Marazita; John R Shaffer; Joanna Wysocka; Mark D Shriver; Seth M Weinberg Journal: Nat Genet Date: 2018-02-19 Impact factor: 38.330
Authors: Anna Doraczynska-Kowalik; Kamil H Nelke; Wojciech Pawlak; Maria M Sasiadek; Hanna Gerber Journal: J Craniofac Surg Date: 2017-07 Impact factor: 1.046
Authors: Leixuri de Frutos-Valle; Conchita Martin; Jose Antonio Alarcon; Juan Carlos Palma-Fernandez; Alejandro Iglesias-Linares Journal: J Evid Based Dent Pract Date: 2018-10-06 Impact factor: 5.267