Genetic Variants Associated With Hidradenitis Suppurativa

被引：35

作者：

Sun, Quan ^{[1
]}

Broadaway, K. Alaine ^{[2
]}

Edmiston, Sharon N. ^{[3
,4
]}

Fajgenbaum, Kristen ^{[3
]}

Miller-Fleming, Tyne ^{[5
]}

Westerkam, Linnea Lackstrom ^{[3
,6
]}

Melendez-Gonzalez, Maria ^{[3
]}

Bui, Helen ^{[7
]}

Blum, Franklin R. ^{[6
]}

Levitt, Brandt ^{[8
]}

Lin, Lan ^{[3
]}

Hao, Honglin ^{[3
]}

Harris, Kathleen Mullan ^{[8
,9
]}

Liu, Zhi ^{[3
,4
]}

Thomas, Nancy E. ^{[3
,8
]}

Cox, Nancy J. ^{[5
]}

Li, Yun ^{[1
,2
]}

Mohlke, Karen L. ^{[2
]}

Sayed, Christopher J. ^{[3
,10
]}

机构：

[1] Univ North Carolina Chapel Hill, Dept Biostat, Chapel Hill, NC USA

[2] Univ North Carolina Chapel Hill, Dept Genet, Chapel Hill, NC USA

[3] Univ North Carolina Chapel Hill, Dept Dermatol, Sch Med, Chapel Hill, NC USA

[4] Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA

[5] Vanderbilt Univ, Dept Med, Div Genet Med, Med Ctr, Nashville, TN USA

[6] Univ North Carolina Chapel Hill, Sch Med, Chapel Hill, NC USA

[7] Univ North Carolina Chapel Hill, Dept Internal Med, Sch Med, Chapel Hill, NC USA

[8] Univ North Carolina Chapel Hill, Carolina Populat Ctr, Chapel Hill, NC USA

[9] Univ North Carolina Chapel Hill, Sociol Dept, Chapel Hill, NC USA

[10] Univ N Carolina, Dept Dermatol, 410 Market St,Ste 400, Chapel Hill, NC 27516 USA

来源：

JAMA DERMATOLOGY | 2023年 / 159卷 / 09期

关键词：

BIOBANK; INSIGHTS; MODEL; SOX9; TOOL; LD;

D O I：

10.1001/jamadermatol.2023.2217

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

IMPORTANCE Hidradenitis suppurativa (HS) is a common and severely morbid chronic inflammatory skin disease that is reported to be highly heritable. However, the genetic understanding of HS is insufficient, and limited genome-wide association studies (GWASs) have been performed for HS, which have not identified significant risk loci. OBJECTIVE To identify genetic variants associated with HS and to shed light on the underlying genes and genetic mechanisms. DESIGN, SETTING, AND PARTICIPANTS This genetic association study recruited 753 patients with HS in the HS Program for Research and Care Excellence (HS ProCARE) at the University of North Carolina Department of Dermatology from August 2018 to July 2021. A GWAS was performed for 720 patients (after quality control) with controls from the Add Health study and then meta-analyzed with 2 large biobanks, UK Biobank (247 cases) and FinnGen (673 cases). Variants at 3 loci were tested for replication in the BioVU biobank (290 cases). Data analysis was performed from September 2021 to December 2022. MAIN OUTCOMES AND MEASURES Main outcome measures are loci identified, with association of P < 1 x 10-8 considered significant. RESULTS A total of 753 patients were recruited, with 720 included in the analysis. Mean (SD) age at symptom onset was 20.3 (10.57) years and at enrollment was 35.3 (13.52) years; 360 (50.0%) patients were Black, and 575 (79.7%) were female. In ameta-analysis of the 4 studies, 2 HS-associated loci were identified and replicated, with lead variants rs10512572 (P = 2.3 x 10-11) and rs17090189 (P = 2.1 x 10-8) near the SOX9 and KLF5 genes, respectively. Variants at these loci are located in enhancer regulatory elements detected in skin tissue. CONCLUSIONS AND RELEVANCE In this genetic association study, common variants associated with HS located near the SOX9 and KLF5 genes were associated with risk of HS. These or other nearby genesmay be associated with genetic risk of disease and the development of clinical features, such as cysts, comedones, and inflammatory tunnels, that are unique to HS. New insights into disease pathogenesis related to these genesmay help predict disease progression and novel treatment approaches in the future.

引用

页码：930 / 938

页数：9

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