Glutathione S-transferase polymorphisms in allergic contact dermatitis to xenobiotics

Background: Xenobiotics, such as para-phenylenediamine (PPD), are thought to be detoxified by phase II enzymes, like the Glutathione S-transferases (GSTs). The human cytosolic GSTs display polymorphisms which are likely to contribute to interindividual differences in responses to xenobiotics. By performing an association study as well as a meta-analysis, we examined the role of GST polymorphisms in allergic contact dermatitis (ACD) to PPD and other xenobiotics. Objectives: First, to investigate the relationship between GSTT1 and GSTM1 deletions and a GSTP1∗A313G polymorphism and ACD to PPD, and secondly to perform a meta-analysis of the three studies concerning the association of these genetic variants and ACD. Methods: The association study used a German case-control set, including 150 cases and 202 controls. Genotyping was performed using a real-time polymerase chain reaction assay. The metaanalysis comprised three studies on ACD to xenobiotics, and totally included 251 cases and 503 controls. In order to determine a possible synergic effect of a combined deletion, the combined GSTT1/GSTM1 genotype was determined additionally. Results: The GSTT1∗0 polymorphism was significantly more frequent in controls (22.50%) compared to ACD patients (13.50%), yielding an OR of 0.54 (95% CI 0.30-0.96, P = 0.036). Neither GSTM1∗0 (OR 1.00, 95% CI 0.65-1.54, P = 1.00), nor the combined deleted GSTT1-/GSTM1- genotype (OR 0.59, 95% CI 0.26-1.35, P = 0.20) was significantly associated with ACD. GSTP∗313 genotypes were not significantly different in ACD patients compared to controls. In the meta-analysis no significant relationship was found neither between GSTT1∗0 (pooled OR 1.40, 95% CI 0.45-4.34, P = 0.56) or GSTM1∗0 (pooled OR 1.44, 95% CI 0.87-2.38, P = 0.16), nor between the combined deleted GSTT1/GSTM1 genotype (pooled OR 2.04, 95% CI 0.51-8.18, P = 0.32) and ACD patients. Conclusion: Our data, as well as others, suggest that the glutathione conjugation pathway may not play a major role in the predisposition to ACD

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