Researchers have identified genetic risk loci that contribute to the genetic risk of developing hidradenitis suppurativa (HS).
The research was published in JAMA Dermatology.
“This discovery is highly relevant because these changes may affect nearby genes in a way that leads to improper development of hair follicles and predispose them to the rupture,” said co-senior author Dr. Christopher Sayed, in a press release. “This results in inflammation and chronic wound formation, which are the classic findings of hidradenitis suppurativa.”
Dr. Sayed is an associate professor at the University of North Carolina (UNC) School of Medicine in Chapel Hill, N.C.
According to the researchers, previous studies have shown that as many as one out of every 100 people have HS or about 3.5 million people throughout the U.S., but the exact number is not known. However, research has shown Black women under the age of 40 have the highest risk of developing HS and are 3 times more likely to have the condition than white people.
To better understand the genetic factors behind HS, the research team performed a genome-wide association study (GWAS). This type of study allows researchers to look at the entire genome to find associations between loci and certain traits, such as chronic diseases.
A total of 720 patients in the Hidradenitis Suppurativa Program for Research and Care Excellence (ProCARE) at UNC’s Department of Dermatology participated in the study and provided saliva and blood samples.
Researchers then integrated the genetic information from the ProCARE patients with controls from the National Longitudinal Study of Adolescent to Adult Health (AddHealth) study, a large longitudinal study of 20,000 adolescents in the United States. Data from biological and genetic samples from Finland (FinnGen), the United Kingdom (UK BioBank) and the Vanderbilt University Medical Center (BioVU) were also used.
The investigators found genetic variants pointing to two genes, SOX9 and KLF5, which are thought to play a role in hair follicle and epidermal development. Certain mutations at these loci were more likely to be found in patients with HS than in patients without HS. According to the release, this is the first report of its kind to successfully identify risk loci for HS.
SOX9 has two functions in the body: maintaining the structure of the hair follicle and assigning stem cells to differentiate into the cells that line the hair follicle. This gene also triggers the activation of three other genes: MMP1, MMP2, and IL-8, which are linked to the formation of basal cell carcinomas, melanomas, and inflammation.
The other suspected gene, KLF5, promotes the generation of keratinocytes and the secretion of enzymes that remove dead skin cells. If unchecked, the body produces so much keratin that the epidermis becomes thick and hair follicles can become blocked.
“While more studies are needed to understand how DNA variants near SOX9 and KLF5 contribute to the pathophysiology of HS, both genes are potentially highly relevant and have not previously been linked to the condition,” said Karen L. Mohlke, PhD, another co-senior author who is also a member of the UNC Lineberger Comprehensive Care Center.
The authors note that KLF5 functions to keep epidermal stem cell levels in check, and SOX9 does the same for hair follicle stem cells. As a result, a potential disruption of the expression of these genetic factors could explain why the body forms chronic wounds in HS.