Abstract

Background: Acne vulgaris, a chronic dermatological condition, affects over 85% of adolescents and often persists into adulthood, ranking as the eighth most prevalent skin disease globally, with an estimated prevalence of 9.38% across all age groups. In Vietnam, the prevalence among adolescents ranges from 80-90%. Beyond physical manifestations such as scarring and aesthetic impairment, acne significantly impacts mental health, contributing to depression, social anxiety, and reduced quality of life. Genetic factors play an important role in determining both acne phenotype and scar formation. This study investigates the association between specific gene variants and acne clinical presentations and scar characteristics.

Methods: This study investigates the correlation between acne phenotypes, inflammatory severity, scar size, and genetic variants of IL1A, TLR4, TNF, FLG, SPINK5, and CYB5R1. A cohort of 202 acne patients was analyzed, categorizing acne phenotypes (non-inflammatory, mixed, inflammatory, cystic) and pore sizes (small, medium, large). Mutation rates of the target genes were assessed using molecular techniques, and statistical significance was determined via paired t-tests, with p-values ≤ 0.05 indicating significant differences. Data were compared with existing literature to contextualize findings.

Results: Non-inflammatory acne exhibited the highest mutation rate for SPINK5 (31.03%), while inflammatory and cystic acne showed elevated mutation rates for IL1 (41.3%), TNF (34.79%), and CYB5R1 (34.78%). TLR4 and FLG mutations were prevalent across all acne phenotypes, with TLR4 peaking in mixed acne (45.29%) and FLG in inflammatory/cystic acne (36.96%). Regarding scar formation, SPINK5 and TNF were associated with small scars, FLG with medium scars, and TLR4 with large scars, all with statistically significant differences (p ≤ 0.05). These findings align with prior studies, such as meta-analyses confirming IL1A rs1800587’s role in acne risk and TNF rs1800629’s protective effect against severe acne. The high mutation rate of TLR4 in inflammatory acne supports its role in sebocyte-driven inflammation, while FLG and SPINK5 mutations suggest impaired skin barrier function contributes to acne and scarring. CYB5R1’s association with inflammatory acne introduces a novel link to lipid metabolism.

Conclusion: This study elucidates the complex interplay between genetic variants, acne phenotypes, and scar formation, highlighting distinct roles for IL1, TNF, and TLR4 in inflammatory acne, FLG and SPINK5 in skin barrier dysfunction, and CYB5R1 in lipid metabolism. These findings underscore the potential for personalized acne treatments targeting specific genetic pathways, such as anti-inflammatory therapies for IL1/TNF-driven acne or barrier-enhancing interventions for FLG/SPINK5-related cases. Further functional studies and larger, diverse cohorts are needed to validate these associations and explore therapeutic applications, paving the way for precision medicine in acne management.