ISSN:
1432-1246
Keywords:
Key words Glutathione S-transferase
;
Polymorphism
;
Thimerosal
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s004200000159
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