Abs Int Arch Occup Environ Health. 2000 73(6) 384-8
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.
Abteilung fur Arbeits- und
Sozialmedizin, Georg-August-Universitat Gottingen, Germany.
gwestph@gwdg.de
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.