This document summarizes a study investigating the association between genetic polymorphisms of the glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) enzymes and risk of developing vitiligo. The study found that vitiligo patients were more likely to have a "double null" genotype where both the GSTM1 and GSTT1 genes were inactive, compared to healthy controls. This suggests the GSTM1/GSTT1 double null genotype may be a genetic risk factor for vitiligo by reducing the body's ability to detoxify harmful compounds through glutathione conjugation. Future research is needed to better understand how GST polymorphisms may contribute to vitiligo pathogenesis through interactions between

1. POLYMORPHISMS OF GLUTATHIONE S-TRANSFERASE M1 AND T1: GENETIC RISK FACTOR FOR VITILIGO Fabrizio Guarneri 1 , Alessio Asmundo 2 , Daniela Sapienza 2 , Serafinella Patrizia Cannavò 1 1 Section of Dermatology and 2 Section of Legal Medicine, Department of Territorial Social Medicine, University of Messina, AOU “G. Martino”, Messina, Italy The International School of Vitiligo and Pigmentary Disorders Barcelona, 2-5 November 2011

2. GLUTATHIONE S-TRANSFERASE

4. NULL GENOTYPES IN GENERAL POPULATION GSTM1 GSTT1 Asmundo et al. 54.67% 24.67% Griffiths et al. 36% 8% Ada et al. 51.9% 17.3% Uhm et al. 51.4% 52.6%

7. AIM OF THE STUDY To define the possible role of the GSTM1 and/or GSTT1 “null” genotype as a risk factor for the development of vitiligo in a population of patients from a Mediterranean area (Sicily and Calabria)

11. RESULTS Genotype GSTM1 Null Active Patients 35 23 Controls 82 68 p = 0.459 GSTT1 Null Active Patients 22 36 Controls 19 113 p = 0.057

12. RESULTS GSTM1 GSTT1 Patients Controls active active 15 49 active null 8 19 p = 0.535 null active 21 64 p = 0.858 null null 14 18 p = 0.041

14. Autoimmune Toxic Neurogenic VITILIGO: PATHOGENIC HYPOTHESES

15. Kostyuk VA et al., Antioxid Redox Signal 2010 We found significantly suppressed mRNA and protein expression of GST M1 isoform, and higher-than-normal levels of both 4-hydroxy-2-nonenal (HNE)-protein adducts and H 2 O 2 in the cultures of keratinocytes derived from unaffected and affected skin of vitiligo patients The broad spectrum of major cytokines, chemokines, and growth factors was dysregulated in both blood plasma and cultured keratinocytes of vitiligo patients Exogenous HNE added to normal keratinocytes induced a vitiligo-like cytokine pattern, and H 2 O 2 overproduction accompanied by adaptive upregulation of catalase and GSTM1 genes