Genetics of Hidradenitis Suppurativa

In April 2020, a review was conducted on the genetics of Hidradenitis Suppurativa (HS), a chronic skin disorder. The prevalence of HS was found to be 0.10% in the United States, with a higher occurrence in females, African Americans, and biracial populations. The study identified 35 unique mutations in genes related to the γ-secretase complex and POGLUT1, an ER O-glucosyltransferase involved in Notch signaling. The response to treatment with adalimumab, a TNFα inhibitor, was potentially influenced by HLA alleles. The research also found that one third of HS patients have a family history of the disorder, suggesting a genetic component. Additionally, the study found a 2.8-fold increase in pathogenic variants of an innate immunity regulator pyrin in patients with complex HS compared to healthy controls. The mutations were found to cause significant 3D structural changes, affect substrate recruitment sites, alter post-translational modifications and disulfide bonds, and significantly reduce levels of NCT and γ-secretase-mediated processing of Notch and signaling in the skin.