What does acne genetics teach us about disease pathogenesis?

Abstract

Summary Background Acne vulgaris is a highly prevalent inflammatory skin disorder with a complex pathogenesis, characterized by comedones, papules, pustules and nodules. Familial preponderance clearly indicates a genetic basis for acne vulgaris, but until recently solid genetic associations were lacking. Results The advent of high‐resolution genotyping array technologies has allowed for large‐scale studies with both family‐based and cross‐sectional designs. These studies have revealed genetic loci encompassing genes that could be active in biological pathways and processes underlying acne vulgaris. However, specific functional consequences of those variants remain elusive. In parallel, investigations into rare disorders and syndromes that incorporate features of acne or acne‐like lesions have recently accelerated our understanding of disease pathogenesis. The genes revealed by these rare disorders highlight mechanisms cardinal for pilosebaceous biology and therefore anchor our insights from genetic association studies for acne vulgaris. Conclusions The next phase of research will require more in‐depth mechanistic investigations of loci and genes implicated in acne phenotypes to define the key molecular players driving the disorder. Concurrently, new treatments for acne vulgaris could be developed by dissecting the candidate molecular pathways to identify druggable targets.

Sebocyte differentiation as a new target for acne therapy: an in vivo experience

“…Overall, our data indicated that an alteration of the sebocyte differentiation process is related to acne development, in agreement with the genetic data on the involvement of the differentiation process of the pilosebaceous unit in the pathogenesis of the disease. 18,44 Low differentiated sebocytes in vitro expressed a higher level of the insulin receptors, an upregulation of the mTOR downstream proteins and lipogenic genes expression, and a reduced concentration of membrane cholesterol, resulting in a higher susceptibility to insulin stimulus. In these cells, insulin induced a signalling pathway leading to a behaviour that resembles the one observed in acne.…”

Recent advances in understanding and managing acne

“…Recent genetic findings have clarified that genes encoding the enzymes 21-hydroxylase ( CYP21A2 ), steroid 5α-reductase type I ( SRD5A1 ), and androgen receptor ( AR ), the somatotropic axis ( GH1, GHR, IGF1, IGFBP3, and IGF1R ), and the forkhead box transcription factor class O1A ( FOXO1A ), peroxisome proliferator-activated receptor ( PPARA, PPARB, PPARG, PPARD ), FGF-2 ( FGF2 ), melanocortin receptor ( MC5R, MC1R ), matrix metalloprotease ( MMP1, MMP2, MMP3, MMP9, MMP13 ), TNF-α ( TNF ), IL-1α ( IL1A ), and Toll-like receptors ( TLR2 and TLR4 ) are implicated in the pathogenesis of acne 13 , 14 .…”

Cutibacterium acnes in acne pathophysiology – the chicken or the egg?

“…Despite enormous progress in molecular techniques the exact pathophysiology of this disease is far from being clear. Some authors claim acne to be an inflammatory disease caused by a Western diet, some emphasize genetic factors, others see Cutibacterium acnes (formerly Propionibacterium acnes ) at the centre of the disease process …”