Genetics and Epigenetics of Keloids.

Significance: Keloid scarring is cosmetically disfiguring, psychosocially distressing, and can be physically disabling. The pathophysiology of keloid formation is poorly understood and subsequently, treatment options are ill defined, limited, and largely unsatisfactory. Therefore, in view of its unsatisfactory and recalcitrant management, keloid therapy is often seen as a financial burden affecting both patients and the health care systems. Recent Advances: Increased research on the genetic and epigenetic mechanisms in keloids has broadened our understanding of keloid pathobiology. Epigenetic mechanisms, mainly DNA methylation, histone modification, and noncoding RNAs, are currently being widely investigated. Advances in genetic sequencing technology and reduced cost have aided this endeavor. Studies on blood and patient-derived keloid tissue are being done with therapeutic agents targeting epigenetic and genetic markers with the shared goal of identifying the pathways underlying the initiation and maintenance of keloids. These advances have informed us of multiple complex molecular pathways implicated in keloids, which are yet to be fully elucidated. Critical Issues: Improved understanding of the genetic and epigenetic causes implicated in keloids will enhance our knowledge of this enigmatic disorder and likely lead to the development of therapeutic targets based on the available clinical and experimental studies. Due to the incomplete knowledge of molecular targets involved in keloid scarring pathways, therapeutics is still lagging for this clinically and scientifically important condition. Future Directions: Focused research on the identification of molecular targets and mechanistic pathways implicated in keloids is required to generate novel antifibrotic therapeutic options to decrease or eradicate recurrence of the disease as well as associated morbidity and improve the quality of life of those affected with keloids.