Glutathione S-transferase M1 (GSTM1) genotype but not GSTT1 or MC1R genotype influences erythemal sensitivity to narrow band (TL-01) UVB phototherapy

Objectives Although a majority of psoriasis patients respond to treatment with narrow band ultraviolet B radiation (TL-01) phototherapy, it is currently not possible to predict erythemal sensitivity, or to identify treatment responders. A variety of antioxidant enzymes, including the polymorphic glutathione S-transferase GSTM1 and GSTT1 genes, protect the cell from UVR-induced oxidative challenge. GSTM1 and GSTT1 are deleted in approximately 50 and 20% of the Caucasian population, respectively, and GST null genotype has been associated with increased sunburn sensitivity and reduced minimal erythemal dose (MED) after broadband UVR exposure in healthy volunteers and with susceptibility to skin cancer. Another polymorphic determinant of UVR sensitivity is the melanocortin 1 receptor (MC1R), which protects cells from UVR-induced apoptosis and photodamage. Our aim was therefore to investigate whether GST or MC1R genotype influenced erythemal sensitivity to narrow band (TL-01) ultraviolet B radiation phototherapy in patients with psoriasis. Methods We used TaqMan quantitative gene copy and allelic discrimination assays to determine GST and MC1R genotypes, and looked for possible associations between genotype and threshold erythemal sensitivity (MED) and treatment outcomes in patients with psoriasis (n=256). Results We showed that GSTM1 genotype, but not GSTT1 or MC1R genotype influences erythemal sensitivity to TL-01 phototherapy, with a significantly lower MED observed in GSTM1 null individuals [χ2(2 d.f.)=8.862, P=0.012]. None of the genotypes studied were associated with TL-01 treatment outcomes or relapse rates. Conclusion GSTM1 genotype may have clinical utilityin the prediction of photosensitivity and/or in identifying patients at increased risk of treatment-related side effects.