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Homozygous gene deletions of the glutathione S-transferases M1 and T1 are
associated with thimerosal sensitization
Westphal GA, Schnuch A, Schulz TG, Reich K, Aberer W, Brasch J, Koch P,
Wessbecher R, Szliska C, Bauer A, Hallier E.
Int Arch Occup Environ Health. 2000 Aug;73(6):384-8.
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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 parasubstituted 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 Stransferase
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.
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