RGD Reference Report - Homozygous gene deletions of the glutathione S-transferases M1 and T1 are associated with thimerosal sensitization. - Rat Genome Database

RGD Reference Report - Homozygous gene deletions of the glutathione S-transferases M1 and T1 are associated with thimerosal sensitization. - Rat Genome Database

Submit Data | Help | Video Tutorials | News | Publications | Download | REST API | Citing RGD | Contact

Advanced Search (OLGA)

General

Homozygous gene deletions of the glutathione S-transferases M1 and T1 are associated with thimerosal sensitization.
Authors:	Westphal, GA Schnuch, A Schulz, TG Reich, K Aberer, W Brasch, J Koch, P Wessbecher, R Szliska, C Bauer, A Hallier, E
Citation:	Westphal GA, etal., Int Arch Occup Environ Health. 2000 Aug;73(6):384-8.
RGD ID:	5491000
Pubmed:	PMID:11007341 (View Abstract at PubMed)
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.

Only show annotations with direct experimental evidence (0 objects hidden)

Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
GSTM1	Human	drug allergy	susceptibility	IAGP		DNA:deletion: :	RGD
GSTT1	Human	drug allergy	susceptibility	IAGP		DNA:deletion: :	RGD
Gstm1	Rat	drug allergy	susceptibility	ISO	GSTM1 (Homo sapiens)	DNA:deletion: :	RGD
Gstm1	Mouse	drug allergy	susceptibility	ISO	GSTM1 (Homo sapiens)	DNA:deletion: :	RGD
Gstt1	Rat	drug allergy	susceptibility	ISO	GSTT1 (Homo sapiens)	DNA:deletion: :	RGD
Gstt1	Mouse	drug allergy	susceptibility	ISO	GSTT1 (Homo sapiens)	DNA:deletion: :	RGD

Genes (Rattus norvegicus)


Gstm1 (glutathione S-transferase mu 1)	Gstt1 (glutathione S-transferase theta 1)

Genes (Mus musculus)


Gstm1 (glutathione S-transferase, mu 1)	Gstt1 (glutathione S-transferase, theta 1)

Genes (Homo sapiens)


GSTM1 (glutathione S-transferase mu 1)	GSTT1 (glutathione S-transferase theta 1)