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Introduction: vitiligo is the result of the interaction of genetic, biochemical, environmental and immunological factors. Oxidative stress has a significant pathogenic role in vitiligo, and is normally contrasted by various non-enzymatic and enzymatic antioxidant systems, including glutathione S-transferases (GSTs). The “null” allele (which causes the lack of production of the corresponding protein) of GST isoforms M1 and T1 may be found, with inter-ethnically variable frequency, in a relevant part of the general population, and is associated to various oxidative-stress related diseases.
Aims & Scope: to define the prevalence of GSTM1 and GSTT1 null polymorphisms in vitiligo patients and healthy controls from Sicily and Calabria, and the correlation of such genotypes with the disease.
Material and Methods: polymerase chain reaction was performed on buccal swabs of 58 non-segmental vitiligo patients (28 males, 30 females) and 150 healthy controls (71 males, 79 females) to define their GSTM1 and GSTT1 genotype (null/active).
Results: the GSTM1/GSTT1 double-null genotype is significantly more frequent in vitiligo patients than in controls (p=0.041), while this is not true for either single-null genotype. Neither the GSTM1 genotype nor the GSTT1 genotype are correlated to the disease.
Comments: the two other papers on GSTM1/GSTT1 genotype and vitiligo agree with our data for which concerns the association of the double-null genotype with a significantly increased risk for the disease, while they differ about disease correlation with either GST null genotype (GSTM1 in one paper, GSTT1 in another, none of the above in our casuistic). Discrepancies are probably due to a different “genetic setup” of the populations studied, which determines a different relative importance of GSTM1 and GSTT1 in the global balance of the antioxidant system. Thus, possession of the null allele for one GST isoform can variably increase the risk for vitiligo, depending on the relative importance of that isoform, while the reduction of the antioxidant potential due to the simultaneous lack of both GST isoforms (double null genotype) is significant in any configuration of the antioxidant system and always constitutes a risk factor for the disease.
Oxidative stress and antioxidant response could be linked to the dysregulated response observed in vitiligo. As suggested in a recent paper, cultured keratinocytes derived from vitiligo patients have higher levels of reactive oxygen species (ROS) and a characteristic dysregulation of the cytokine, chemokine and growth factor pattern.
Future perspectives include :
- GST genotyping of other populations, ethnically different from those currently described in literature, because of the high variability of the frequency of GST - Disclaimer-
This PPT is loaded as student material "as is", from the VRF Vitiligo Master Class Barcelona November 2011; VRF does not endorse or otherwise approve it.