Molecular Genetic Predictors of Post-Acne Pathological Scar Formation: A Systematic Review

Post-acne sequelae represent a clinically significant outcome of acne that may result in persistent structural skin changes and impaired quality of life. Despite the established heritability of acne, direct studies of genetic predictors of post-acne scarring remain limited, highlighting the need to systematically synthesize the available evidence. A systematic literature search was conducted in the PubMed/MEDLINE, Scopus, and Web of Science Core Collection databases from 2016 to 2026 in accordance with the PRISMA 2020 guidelines. Original human studies evaluating genetic factors associated with post-acne scarring and severe acne were included. Studies of candidate genes and genetic polymorphisms, genome-wide association studies (GWAS), as well as studies evaluating genetically determined alterations involved in extracellular matrix remodeling and inflammatory responses were considered. In addition, data from epigenetic, transcriptomic, miRNA, proteomic, and Mendelian randomization studies were taken into account when interpreting the findings. Direct studies identified associations between scarring and variants in genes involved in extracellular matrix remodeling, including MMP2 and TIMP2. The MMP2 -1306 CC genotype was predominantly associated with hypertrophic scarring, whereas the TIMP2 rs4789932 variant was associated with the risk and severity of scarring. Increased levels of miR-21, miR-150, and miR-223 were associated with a predisposition to atrophic scarring. Indirect evidence from genetic studies of acne indicates the involvement of genes related to inflammatory responses, steroidogenesis, oxidative stress, lipid metabolism, and extracellular matrix remodeling. GWAS further identified loci associated with pilosebaceous unit development, Wnt and TGF-β signaling, immune-inflammatory processes, and extracellular matrix remodeling. Epigenetic and proteomic studies further supported the potential role of gene expression regulation and individual mediators in the development of a severe acne phenotype. Post-acne scar formation is likely determined by a combination of the clinical severity of inflammation and interindividual, genetically determined variability in immune responses and tissue repair. Currently, no validated genetic markers for post-acne scarring risk are available for routine clinical use. Their validation requires large, multicenter, standardized studies accounting for morphological scar types and integrating genomic, transcriptomic, and epigenomic data.