Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Westphal, GA; Schnuch, A; Schulz, TG; Reich, K; Aberer, W; Brasch, J; Koch, P; Wessbecher, R; Szliska, C; Bauer, A; Hallier, E.
Homozygous gene deletions of the glutathione S-transferases M1 and T1 are associated with thimerosal sensitization.
Int Arch Occup Environ Health. 2000; 73(6):384-388
Doi: 10.1007%2Fs004200000159
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- Co-Autor*innen der Med Uni Graz
- Aberer Werner
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- Abstract:
- OBJECTIVE: Thimerosal is an important preservative in vaccines and ophthalmologic preparations. The substance is known to be a type IV sensitizing agent. High sensitization rates were observed in contact-allergic patients and in health care workers who had been exposed to thimerosal-preserved vaccines. There is evidence for the involvement of the glutathione system in the metabolism of thimerosal or its decomposition products (organomercury alkyl compounds). Thus detoxification by polymorphically expressed glutathione S-transferases such as GSTT1 and GSTM1 might have a protective effect against sensitization by these substances. METHODS: To address this question, a case control study was conducted, including 91 Central European individuals with a positive patch-test reaction to thimerosal. This population was compared with 169 healthy controls and additionally with 114 individuals affected by an allergy against para-substituted aryl compounds. The latter population was included in order to test whether possible associations were due to substance-specific effects, or were a general feature connected with type IV immunological diseases. Homozygous deletions of GSTT1 and GSTM1 were determined by polymerase chain reaction. RESULTS: Glutathione S-transferase M1 deficiency was significantly more frequent among patients sensitized to thimerosal (65.9%, P = 0.013) compared with the healthy control group (49.1%) and the "para-compound" group (48%, P = 0.034). Glutathione S-transferase T1 deficiency in the thimerosal/mercury group (19.8%) was barely elevated versus healthy controls (16.0%) and the "para-compound" group (14.0%). The combined deletion (GSTT1-/GSTM1-) was markedly more frequent among thimerosal-sensitized patients than in healthy controls (17.6% vs. 6.5%, P = 0.0093) and in the "para-compound" group (17.6% vs. 6.1%, P =0.014), revealing a synergistic effect of these enzyme deficiencies (healthy controls vs. thimerosal GSTM1 negative individuals, OR = 2.0 [CI = 1.2-3.4], GSTT1-, OR = 1.2 [CI = 0.70-2.1], GSTM1/T1-, OR = 3.1 [CI = 1.4-6.5]). CONCLUSIONS: Since the glutathione-dependent system was repeatedly shown to be involved in the metabolism of thimerosal decomposition products, the observed association may be of functional relevance.
- Find related publications in this database (using NLM MeSH Indexing)
- Adolescent -
- Adult -
- Aged -
- Child -
- Drug Hypersensitivity - immunology
- Female - immunology
- Gene Deletion - immunology
- Glutathione Transferase - genetics
- Humans - genetics
- Male - genetics
- Middle Aged - genetics
- Polymorphism, Genetic - genetics
- Preservatives, Pharmaceutical - adverse effects
- Thimerosal - adverse effects
- Find related publications in this database (Keywords)
- glutathione S-transferase
- polymorphism
- thimerosal