Genetic variation involved in the risk to external apical root resorption in orthodontic patients: a systematic review.

Objective: To perform a systematic review/meta-analysis to elucidate the scientific basis for the association between genetic variations and risk of external apical root resorption (EARR) in orthodontic patients.

Materials And Methods: Four databases (PubMed, Web of Science, Scopus, LILACS) were electronically searched until November 22, 2020, followed by manual and gray literature search. Case-control or cross-sectional studies that evaluated genes involved in the susceptibility of orthodontic patients to EARR were eligible. Two reviewers applied the inclusion and exclusion criteria, extracted qualitative data, as well as assessed methodological quality using instrument proposed for genetic studies. For synthesis results, narrative and quantitative data (meta-analysis) were performed. The certainty of the evidence was tested using the GRADE Working Group approach.

Results: Of 201 articles in total, 16 studies were included in the review. Of these, 11 presented moderate and 5 of high methodological quality. In the narrative analysis, from 16 studies, 15 studies (10 genes) showed a significant association with EARR and 9 studies were included in the meta-analysis. Only the polymorphism rs208294 in P2RX7 (dominant model) was associated with EARR (OR = 0.52, 95%CI = 0.29-0.95, p = 0.03) and presented a very low certainty of the evidence.

Conclusion: Narrative analyses of individual studies demonstrated an association of many genes. The number of studies for each genetic variation was very low, and methodological heterogeneity between the studies was observed. Quantitative analyses (meta-analysis) could only show an involvement for P2RX7 (rs208294) in the risk of orthodontic patients to EARR at a very low certainty of evidence. (CRD42018085411).

Clinical Relevance: The knowledge regarding the molecular aspects involved in the etiology of EARR will allow orthodontists to use a personalized treatment and early diagnosis of risk patients. This systematic review demonstrates that more studies are necessary to unravel the role of genetic variation for patients' risk to EARR during orthodontic tooth movement.