What Does Acne Genetics Teach Us About Disease Pathogenesis?

The 2019 review article explores the genetic underpinnings of acne vulgaris, a prevalent inflammatory skin condition, revealing a significant hereditary component with heritability estimates up to 78%. It discusses the identification of various genetic loci through genome-wide association studies (GWAS), which are linked to biological pathways such as androgen metabolism, inflammation, stem cell fate, and tissue remodeling. Despite these findings, the functional implications of these genetic variants remain unclear. The review calls for more in-depth research to understand the molecular mechanisms driving acne and to develop targeted treatments. It also notes the variation in genetic associations across different ethnicities and the psychological and social impact of the condition. The document reviews monogenic disorders that cause severe acne, which can shed light on acne vulgaris pathogenesis and treatment targets. Furthermore, it highlights the Notch signaling pathway's role in sebaceous gland function and the association of hormonal imbalances in conditions like PCOS and CAH with acne. The review emphasizes that while severe acne has been the focus of most genetic studies, more research on mild-to-moderate acne is needed, along with the development of cell-based models for treatment discovery. It concludes with optimism for targeted acne treatments based on genetic research, suggesting that inflammation may be a secondary event in acne development.