Genetics and Epigenetics of Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is a complex disease with likely multifactorial etiologies, including genetic, epigenetic, immunologic, microbiologic, endocrine, and environmental. Here we review the gamut of prior genetic studies encompassing family linkage analyses, target candidate gene studies, and one genome-wide association study. To date, these studies have identified over 50 genetic variants suspected to confer disease susceptibility, disease sub-phenotype, or treatment response. Whereas some of these presumed pathogenic variants reside in genes encoding gamma-secretase, a multi-protein complex with a role in epidermal differentiation and homeostasis, many other genes have been implicated as well. Research regarding the epigenetics of HS is preliminary, however early studies have identified altered DNA hydroxymethylation and miRNA expression in HS lesions. While the degree to which genetics and epigenetics play a role in HS pathogenesis is difficult to answer, further evaluation of genetic and epigenetic alterations and their downstream effects could help with identifying novel therapeutic targets. Additionally, research linking genotype to phenotype or patient response to specific treatment could prove clinically useful and lead to more personalized medicine in HS management.