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Contact Hypersensitivity as a Murine Model of Allergic Contact Dermatitis
Published on: September 26, 2022
Genetic Basis of Irritant Susceptibility in Health Care Workers
Berran Yucesoy1, Yerkebulan Talzhanov, M Michael Barmada
1Health Effects Laboratory Division (Drs Yucesoy, Kashon, Ms Frye, Wang, Ms Fluharty, Dr Meade), CDC/NIOSH, Morgantown, West Virginia; Department of Human Genetics (Drs Talzhanov and Barmada), University of Pittsburgh, Pennsylvania; BRT-Burleson Research Technologies (Dr Johnson), Morrisville, North Carolina; University Hospitals Case Medical Center (Drs Baron and Nedorost), Case Western Reserve University, Cleveland, Ohio; Department of Pediatrics, School of Medicine (Dr Wilson), University of Nevada, Reno; Department of Dermatology, School of Medicine (Dr Gharib), West Virginia University, Morgantown; Toxicology Branch, DNTP/NIEHS (Dr. Germolec), Research Triangle Park, North Carolina; and School of Public Health (Dr Luster), West Virginia University, Morgantown.
Objective:
The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) within genes involved in inflammation, skin barrier integrity, signaling/pattern recognition, and antioxidant defense with irritant susceptibility in a group of health care workers.
Methods:
The 536 volunteer subjects were genotyped for selected SNPs and patch tested with three model irritants: sodium lauryl sulfate (SLS), sodium hydroxide (NaOH), and benzalkonium chloride (BKC). Genotyping was performed on genomic DNA using Illumina Goldengate custom panels.
Results:
The ACACB (rs2268387, rs16934132, rs2284685), NTRK2 (rs10868231), NTRK3 (rs1347424), IL22 (rs1179251), PLAU (rs2227564), EGFR (rs6593202), and FGF2 (rs308439) SNPs showed an association with skin response to tested irritants in different genetic models (all at P < 0.001). Functional annotations identified two SNPs in PLAU (rs2227564) and ACACB (rs2284685) genes with a potential impact on gene regulation. In addition, EGF (rs10029654), EGFR (rs12718939), CXCL12 (rs197452), and VCAM1 (rs3917018) genes showed an association with hand dermatitis (P < 0.005).
Conclusions:
The results demonstrate that genetic variations in genes related to inflammation and skin homeostasis can influence responses to irritants and may explain inter-individual variation in the development of subsequent contact dermatitis.
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