What does acne genetics teach us about disease pathogenesis?

Abstract

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.