Global insights into keloid formation: An international systematic review of regional genetic risk factors and commonalities

Keloid disorder is a morbid and disfiguring benign fibroproliferative disease with a higher incidence in groups with darker skin pigmentation. Predicting keloidogenesis in patients is difficult with treatment primarily aimed at preventing further scar expansion and improving aesthetics without addre...

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Published in:Wound repair and regeneration Vol. 32; no. 5; pp. 746 - 757
Main Authors: James, Andrew J., Torres‐Guzman, Ricardo A., Chaker, Sara C., Sigel, Matthew E., Perdikis, Galen, Supp, Dorothy M., Dale Slater, Elizabeth L.
Format: Journal Article
Language:English
Published: Hoboken, USA John Wiley & Sons, Inc 03-07-2024
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Summary:Keloid disorder is a morbid and disfiguring benign fibroproliferative disease with a higher incidence in groups with darker skin pigmentation. Predicting keloidogenesis in patients is difficult with treatment primarily aimed at preventing further scar expansion and improving aesthetics without addressing their unknown underlying pathophysiology. We aimed to identify potential genetic predispositions to keloid scarring in the literature. A search was conducted on 21 August 2023, by the first and second authors independently from 1985 to August 2023 using PubMed, MEDLINE, Embase, Web of Science, Scopus and CINAHL. The following MeSH terms were used: ‘Keloid’, ‘Risk’ and ‘Genetic’. Two researchers independently searched for studies based on titles and s and screened filtered articles by reviewing full text. If no agreement could be reached, a third senior author designated whether the article should be included. We used the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses 2020 statement as the basis of our organisation. Human studies with genetic analysis to determine an association of a protein or gene to keloidogenesis were selected for inclusion. Studies in languages other than English, reviews, conference articles, and book chapters were excluded. Fifty studies met inclusion criteria. The human leukocyte antigen (HLA) system was broadly implicated, and the DRB1*15 allele was associated with an increased risk of keloid in three separate ethnic groups. Some HLA Class I alleles were associated with keloid in one population but not in others. Additionally, polymorphisms in the E3 ubiquitin‐protein ligase (NEDD4) signal cascade and vitamin D receptor (VDR) have been implicated in diverse groups. No current genetic test can predict keloid risk. Our review identified candidate predisposing genes, including NEDD4, VDR and components of the HLA system. Further studies in heterogeneous populations are needed to identify reliable screening targets.
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ISSN:1067-1927
1524-475X
1524-475X
DOI:10.1111/wrr.13203