Association of MHC region SNPs with irritant susceptibility in healthcare workers

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.

Keywords:

• Genetics
• healthcare workers
• irritant contact dermatitis
• MHC

Acknowledgements

The authors wish to thank the volunteers who participated in this study. The authors also acknowledge the efforts of Debbie Velickoff from the WVU Pediatrics Department. The authors also thank Drs. Linda Sargent, Scott Auerbach and Ruth Lunn for their critical reviews.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Institute for Occupational Safety and Health.

Funding information

This study was supported in part by an inter-agency agreement between NIOSH and NIEHS (AES12007001-1-0-6) as a collaborative National Toxicology Program research activity.