Association of MHC region SNPs with irritant susceptibility in healthcare workers.
Irritant contact dermatitis is the most common work-related skin disease, especially affecting workers in "wet-work" occupations. This study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) within the major histocompatibility complex (MHC) and skin irritant response in a group of healthcare workers. 585 volunteer healthcare workers were genotyped for MHC SNPs and patch tested with three different irritants: sodium lauryl sulfate (SLS), sodium hydroxide (NaOH) and benzalkonium chloride (BKC). Genotyping was performed using Illumina Goldengate MHC panels. A number of SNPs within the MHC Class I (OR2B3, TRIM31, TRIM10, TRIM40 and IER3), Class II (HLA-DPA1, HLA-DPB1) and Class III (C2) genes were associated (p < 0.001) with skin response to tested irritants in different genetic models. Linkage disequilibrium patterns and functional annotations identified two SNPs in the TRIM40 (rs1573298) and HLA-DPB1 (rs9277554) genes, with a potential impact on gene regulation. In addition, SNPs in PSMB9 (rs10046277 and ITPR3 (rs499384) were associated with hand dermatitis. The results are of interest as they demonstrate that genetic variations in inflammation-related genes within the MHC can influence chemical-induced skin irritation and may explain the connection between inflamed skin and propensity to subsequent allergic contact sensitization.
a Health Effects Laboratory Division , CDC/NIOSH , Morgantown , WV , USA ;
Berran
B
Yucesoy
b Department of Human Genetics, Graduate School of Public Health , University of Pittsburgh , Pittsburgh , PA , USA ;
Yerkebulan
Y
Talzhanov
b Department of Human Genetics, Graduate School of Public Health , University of Pittsburgh , Pittsburgh , PA , USA ;
M
M
Michael Barmada
c BRT-Burleson Research Technologies , Morrisville , NC , USA ;
Victor J
VJ
Johnson
a Health Effects Laboratory Division , CDC/NIOSH , Morgantown , WV , USA ;
Michael L
ML
Kashon
d University Hospitals Case Medical Center, Case Western Reserve University , Cleveland , OH , USA ;
Elma
E
Baron
e Department of Pediatrics, School of Medicine , University of Nevada , Reno , NV , USA ;
Nevin W
NW
Wilson
a Health Effects Laboratory Division , CDC/NIOSH , Morgantown , WV , USA ;
Bonnie
B
Frye
a Health Effects Laboratory Division , CDC/NIOSH , Morgantown , WV , USA ;
Wei
W
Wang
a Health Effects Laboratory Division , CDC/NIOSH , Morgantown , WV , USA ;
Kara
K
Fluharty
f Department of Dermatology, School of Medicine , West Virginia University , Morgantown , WV , USA ;
Rola
R
Gharib
g Office of Director, CDC/NIOSH , Morgantown , WV , USA ;
Jean
J
Meade
h Toxicology Branch, DNTP/NIEHS, Research Triangle Park , NC , USA ;
Dori
D
Germolec
i School of Public Health, West Virginia University , Morgantown , WV , USA.
Michael I
MI
Luster
d University Hospitals Case Medical Center, Case Western Reserve University , Cleveland , OH , USA ;
Susan
S
Nedorost
D000293:Adolescent; D000328:Adult; D000368:Aged; D001548:Benzalkonium Compounds; D003546:Cysteine Endopeptidases / Q000235:genetics*; D017453:Dermatitis, Irritant / Q000235:genetics* / Q000276:immunology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D059868:HLA-DP beta-Chains / Q000235:genetics; D006282:Health Personnel; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012867:Skin / Q000276:immunology*; D012882:Skin Tests; D012967:Sodium Dodecyl Sulfate; D012972:Sodium Hydroxide; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D055815:Young Adult
D001548:Benzalkonium Compounds; D006680:HLA Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; C506929:ITPR3 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; C071313:LMP-2 protein; D012967:Sodium Dodecyl Sulfate; D012972:Sodium Hydroxide; C413363:RNF40 protein, human; D044767:Ubiquitin-Protein Ligases; D003546:Cysteine Endopeptidases
Genetics; MHC; healthcare workers; irritant contact dermatitis