Common variants associated with hidradenitis suppurativa (HS) are: SOX9 and KLF5 These genes are associated with the risk of HS, and these or other adjacent genes are associated with the risk of inherited diseases and the development of clinical manifestations such as cysts, comedones, and inflammatory tunnels characteristic of HS, according to . It is possible that it is related. JAMA Dermatology.
Genetic understanding of HS is limited and few genome-wide association studies (GWAS) have been performed on HS. No significant risk loci have been recognized in existing studies.
“As with all GWAS, this genetic association study identifies associations for variants near candidate genes that have plausible roles in disease biology, but does not allow these variants or genes to contribute to disease risk.” No causal relationship is proven,” the researchers said.
The researchers aimed to identify genetic variants associated with HS and uncover the underlying genetic and genetic mechanisms.
HS is a common, severe, pathologic chronic inflammatory skin disease with high heritability. It is characterized by painful nodules, abscesses, and tunnels, which are common in the interproximal region. Siblings of an affected individual have almost a 20-fold risk of developing HS.
First, from August 2018 to July 2021, a total of 753 HS patients from the HS Program for Research and Care Excellence (HS ProCARE) at the Department of Dermatology at the University of North Carolina were recruited for this genetic association study. recruited.
The GWAS was initiated on 720 patients (after quality control) using controls from the Add Health study, followed by a meta-analysis on two large biobanks, UK Biobank (247) and FinnGen (673). it was done. The BioVU biobank (290 cases) was tested for replication of the 3-locus variant and data analysis was performed from September 2021 to December 2022.
The primary outcome measure identified loci with the following associations: P. < 1×10–8 is considered significant.
A total of 720 patients participated in the analysis. Mean (SD) age at symptom onset was 20.3 (10.57) years and 35.3 (13.52) years at enrollment. 360 patients were black and 575 were female. A meta-analysis of four studies identified and replicated two her loci associated with HS. lead variant rs10512572 (P. = 2.3×10–11) and rs17090189 (P. = 2.1×10–8) SOX9 and KLF5 each gene. Mutants at these loci are found in enhancer regulatory elements identified in skin tissue.
HS candidate gene SOX9encodes SRY-box transcription factor 9, which is highly expressed in the human epidermis and outer root sheath of hair follicles and is essential for hair follicle differentiation and maintenance.of SOX9 genes up-regulate MMP1, MMP2and IL-8, These are associated with tumorigenesis and inflammation. In human colitis, intestinal function is impaired. KLF5 Expression is associated with increased disease severity.
New insights into the pathogenesis of diseases associated with these genes may help predict disease progression and future novel therapeutic approaches. Furthermore, genetic correlations between HS and common comorbidities such as psoriasis, inflammatory bowel disease and type 2 diabetes suggest that common genetic mechanisms may predispose to risk. The researchers recommend that further investigations using more robust HS GWAS are needed to examine other comorbidities and clarify common risk mechanisms.
The researchers also said functional studies should examine whether HS-associated mutations and surrounding regulatory elements may be altered. SOX9 and KLF5 Altered function or expression, which subsequently influences HS pathology. These genes are strong candidates because they influence hair follicles, epidermal differentiation and inflammation.Other flanking genes are like KLF12 can also play a role. Larger sample sizes and sequencing are needed to identify rare genetic variants involved in small numbers of patients, such as γ-secretase complex variants.
This study has some limitations. Some of her Add Health participants may have had HS, which may lead to misclassification bias against nulls. Although the HS ProCARE included patients with European and African ancestry, the small sample size precluded the identification of significant loci within ancestry groups and the assessment of generalizability in other ancestry. limited the ability of researchers to perform
“Ultimately, understanding how genes drive tunneling and exaggerated inflammatory responses may lead to therapeutic breakthroughs in targeting the pathogenesis of HS.” the researchers concluded.
Sun Q, Broadway KA, Edmiston SN, et al. Genetic mutations associated with hidradenitis suppurativa. JAMA Dermatol. Published online on July 26, 2023. doi:10.1001/jamadermatol.2023.2217
[This article was originally published by our sister brand, AJMC.]