HLA-B*1301 as a Biomarker for Genetic Susceptibility to Hypersensitivity Dermatitis Induced by Trichloroethylene among Workers in China

Abstract

BackgroundTrichloroethylene (TCE) is used extensively as an industrial solvent and has been recognized as one of the major environmental pollutants. To date, > 200 cases of TCE-induced hypersensitivity dermatitis among exposed workers have been reported worldwide, and TCE exposure has become one of the critical occupational health issues in Asia.ObjectivesThe study aimed to identify genetic susceptible biomarkers associated with the TCE-induced hypersensitivity dermatitis in genes located in the human leukocyte antigen (HLA) region.MethodsFrom 1998 to 2006, 121 cases with TCE-induced hypersensitivity dermatitis and 142 tolerant controls were recruited into the population-based case–control study. We determined HLA alleles B, DRB1, DQA1, and DQB1, by sequence-based typing. p-Values were corrected for comparisons of multiple HLA alleles. In addition, we compared and analyzed the structure character of amino acid residues of HLA molecules found in participants.ResultsWe obtained complete genotyping data of 113 cases and 142 controls. The allele HLA-B*1301 was present in 83 (73.5%) of 113 patients compared with 13 (9.2%) of 142 tolerant workers (odds ratio = 27.5; 95% confidence interval, 13.5–55.7; corrected p = 1.48 × 10−21). In addition, the HLA-B*44 alleles were present in 6.2% (7/113) of patients, but were absent in TCE-tolerant workers. Residue 95 shared by HLA-B*1301 and HLA-B*44 molecules formed a different pocket F than other residues.ConclusionsThe allele HLA-B*1301 is strongly associated with TCE-induced hypersensitivity dermatitis among exposed workers and might be used as a biomarker to predict high risk individuals to TCE.

Hypersensitivity syndrome due to trichloroethylene exposure: A severe generalized skin reaction resembling drug‐induced hypersensitivity syndrome

“…Recently, human leukocyte antigen (HLA)-B*1301 was identified as a marker of individual susceptibility to TCE-induced HS, with an odds ratio of 27.5 in a patient group in China. 28 This finding is analogous to that in carbamazepine-induced Stevens-Johnson syndrome and allopurinol-induced severe cutaneous adverse reactions, including DIHS, which have strong associations with HLA-B*1502 and HLA-B*5801, respectively. 29,30 In China, the allele frequency of HLA-B*1301 is higher in the southern population (10%) than in the northern population (3-4%), and this is may be a major factor explaining the mass outbreak of TCE-induced hypersensitivity dermatitis in the southern population.…”

“…29,30 In China, the allele frequency of HLA-B*1301 is higher in the southern population (10%) than in the northern population (3-4%), and this is may be a major factor explaining the mass outbreak of TCE-induced hypersensitivity dermatitis in the southern population. 28 The allele frequency in Japan is 1.3%, 31 which is even lower than in the Han population in northern China and may partly explain why there have been fewer cases in Japan than in China. 7 Additionally, HLA-B*44 was demonstrated to be related to TCE-induced HS.…”

“…Li reported that HLA-B*44 was present 6.2% of 113 patients, but was not observed in any of the 142 TCE-tolerant workers. 28 …”

Effects of Genetic Polymorphisms of N-Acetyltransferase on Trichloroethylene-Induced Hypersensitivity Dermatitis among Exposed Workers

“…We have investigated the relation between polymorphisms of Tumor Necrosis Factor (TNF) and Interleukin (IL)-4 gene and the risk of TCE-induced hypersensitivity dermatitis, the results reveal that individuals with a heterozygous genotype of TNFα-308 were associated with the decreased risk of the disease relative to the homozygous genotype 18) . Li et al reported the Human Lymphocyte Antigen (HLA)-B*1301 is strongly associated with the disease among exposed workers and might be used as a biomarker to predict high risk individuals to TCE 19) . However, there is no study on the susceptible biomarkers in TCE metabolic process, which is as one of the basic biologic events in the development of TCE-induced hypersensitivity dermatitis.…”

Trichloroethylene Causes Generalized Hypersensitivity Skin Disorders Complicated by Hepatitis

“…If a worker does not suffer from the disorders by the end of the 3rd month after the start of exposure, he/she is not susceptible. The incidence of the disorders in Guangdong Province is estimated to be less than 1 case per one hundred exposed workers 9) , and recently, human leukocyte antigen (HLA)-B*1301 and HLA-B*44 were identified as markers of individual susceptibility with an odds ratio of 36.8 in the patient group for having either of the HLA loci 15) . This is a finding analogous to carbamazepine-induced SJS/ TEN and allopurinol-induced severe cutaneous adverse reactions in which their strong associations with HLA-B*1502 16) and HLA-B*5801 17) , respectively, were reported.…”