Association of MHC region SNPs with irritant susceptibility in healthcare workers.

Yucesoy B1, Talzhanov Y2, Michael Barmada M2, Johnson VJ3, Kashon ML1, Baron E4, Wilson NW5, Frye B1, Wang W1, Fluharty K1, Gharib R6, Meade J7,Germolec D8, Luster MI9, Nedorost S4.

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Abstract

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.