Performance of genetic risk factors in prediction of trichloroethylene induced hypersensitivity syndrome

Abstract

Trichloroethylene induced hypersensitivity syndrome is dose-independent and potentially life threatening disease, which has become one of the serious occupational health issues and requires intensive treatment. To discover the genetic risk factors and evaluate the performance of risk prediction model for the disease, we conducted genomewide association study and replication study with total of 174 cases and 1761 trichloroethylene-tolerant controls. Fifty seven SNPs that exceeded the threshold for genome-wide significance (P < 5 × 10−8) were screened to relate with the disease, among which two independent SNPs were identified, that is rs2857281 at MICA (odds ratio, 11.92; Pmeta = 1.33 × 10−37) and rs2523557 between HLA-B and MICA (odds ratio, 7.33; Pmeta = 8.79 × 10−35). The genetic risk score with these two SNPs explains at least 20.9% of the disease variance and up to 32.5-fold variation in inter-individual risk. Combining of two SNPs as predictors for the disease would have accuracy of 80.73%, the area under receiver operator characteristic curves (AUC) scores was 0.82 with sensitivity of 74% and specificity of 85%, which was considered to have excellent discrimination for the disease, and could be considered for translational application for screening employees before exposure.

Irreversible effects of trichloroethylene on the gut microbial community and gut‐associated immune responses in autoimmune‐prone mice

“…Trichloroethylene (TCE) is an industrial solvent and widespread water pollutant most strongly linked to immunotoxicity and autoimmune disease in experimental rodent models (Blossom & Doss, 2007;Cai et al, 2008;Cooper, Makris, Nietert, & Jinot, 2009;Gilbert, Pumford, & Blossom, 2006;Griffin, Blossom, Jackson, Gilbert, & Pumford, 2000;Griffin, Gilbert, Lamps, & Pumford, 2000). There is also evidence to suggest that TCE promotes immune-mediated inflammatory diseases, hypersensitivity and autoimmunity in humans (Cooper et al, 2009;Dai et al, 2015;EPA, 2011;Huang et al, 2015;Khader, Gaffen, & Kolls, 2009;Parks & De Roos, 2014;Zhao et al, 2016). We and others have shown the effect of continuous developmental exposure to TCE in mice encompassing gestation, lactation, and early life generated CD4 + T-cell alterations and/or early signs of tissue inflammation in both normal and autoimmune-susceptible mouse strains (Blossom, Melnyk, Li, Wessinger, & Cooney, 2017;Gilbert, Woodruff, & Blossom, 2014;Peden-Adams et al, 2006;Peden-Adams et al, 2008).…”

Sex-Dependent Effects on Liver Inflammation and Gut Microbial Dysbiosis After Continuous Developmental Exposure to Trichloroethylene in Autoimmune-Prone Mice

“…In extreme cases, some individuals developed a syndrome with severe skin lesions ranging from erythema to exfoliative dermatitis along with toxic epidermal necrolysis accompanying lymphadenopathy and fever. These diverse symptoms were often accompanied by immune-mediated liver injury often termed non-viral hepatitis ( Dai et al, 2015 ). Although the liver manifestations appeared to be T cell-driven, it is not clear whether the immune response was directed toward self as in AIH.…”

Utility evaluation of HLA-B*13:01 screening in preventing trichloroethylene-induced hypersensitivity syndrome in a prospective cohort study

“…Previous case-control studies have found several genetic risk factors associated with TIHS, including human leucocyte antigen ( HLA)-B*13:01 ,10 rs2857281 in the intron of major histocompatibility complex class I chain - related gene A ( MICA ),11 rs2523557 located HLA-B and MICA ,11 N-acetyltransferase-2 ,12 and tumour necrosis factor (TNF)-α 13. However, no systematic prospective study has been conducted to evaluate the performance of genetic biomarkers in reducing the incidence of TIHS and improving the efficiency of occupational health surveillance.…”