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homozygous gene deletions of the glutathione S-transferases
M1 and T1 are associated with thimerosal sensitization
Glutathione Articles - ASD (Autism Spectrum Disorders)
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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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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