Kemp, E.H.

E.H. Kemp

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British Journal of Dermatology

English

The
            <scp>CC</scp>
            genotype of the
            <i>
              <scp>ERCC</scp>
              1
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            C118T single‐nucleotide polymorphism impacts positively on the efficacy of narrowband ultraviolet B therapy for vitiligo

White Rose Research Online

This is a repository copy of The CC genotype of the ERCC1 C118T single-nucleotide polymorphism impacts positively on the efficacy of narrowband ultraviolet B therapy for vitiligo..White Rose Research Online URL for this paper:http://eprints.whiterose.ac.uk/89882/Version: Accepted VersionArticle:Kemp, E.H. (2015) The CC genotype of the ERCC1 C118T single-nucleotide polymorphism impacts positively on the efficacy of narrowband ultraviolet B therapy for vitiligo. British Journal of Dermatology, 173 (2). 324 - 325. ISSN 0007-0963 https://doi.org/10.1111/bjd.13977eprints@whiterose.ac.ukhttps://eprints.whiterose.ac.uk/Reuse Unless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version - refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher’s website. Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. 1  Commentary ʹ The CC genotype of the ERCC1 C118T single-nucleotide polymorphism impacts positively on the efficacy of NB-UVB therapy for vitiligo   Vitiligo is a common depigmenting skin disease with a prevalence of 1-2%.1 Although the exact aetiology and detailed pathogenesis of vitiligo is not fully understood, autoreactive T cell responses against melanocytes are clearly involved in the development of the disease.2,3 Of several immunosuppressive treatments, narrow-band ultraviolet B (NB-UVB) now represents the phototherapy of choice for inducing repigmentation in patients with generalised vitiligo where depigmented areas affect multiple sites or large areas of the body. Indeed, more than 75% repigmentation has been achieved in over 50% of patients.4,5 It is also useful for halting the progression of currently active vitiligo; stabilisation of the disease was evident in 80% of treated patients.5 Comparative studies have indicated also the superior efficacy and better safety profile of NB-UVB over psoralen with UVA.6,7  As yet, the precise mechanism of action of NB-UVB in repigmenting vitiligo lesions is unknown. However, NB-UVB can activate the release from keratinocytes of endothelin-1 and basic fibroblast growth factor, which stimulate melanocyte, and can stimulate the expression of focal adhesion kinase and matrix metalloproteinases, which may enhance melanocyte migration from the outer root sheath of the hair follicle into the epidermis.8 In addition, during NB-UVB irradiation, skin-infiltrating T cells are induced to apoptose due to the accumulation of DNA damage in the form of cyclobutane pyrimidine dimers.9 Repair of such damaged DNA is managed via the nucleotide excision repair (NER) pathway and, interestingly, single-nucleotide polymorphisms of the DNA repair gene APE1 have been associated with susceptibility to vitiligo.10 2   In this issue of the BJD, Dai et al11 investigated whether allelic variants of the NER gene ERCC1 (excision repair cross complementation 1) could influence the efficacy of NB-UVB treatment of vitiligo. Their study of 86 patients with active vitiligo indicated that those with the CC genotype of the ERCC1 C118T single-nucleotide polymorphism demonstrated higher levels of repigmentation as well as an earlier appearance of repigmenting lesions following therapy with NB-UVB. Furthermore, the T lymphocyte apoptosis rate and cyclobutane pyrimidine dimer levels were significantly higher in patients with the CC genotype in comparison to those with the TT and CT gene variants. Overall, this interesting study provides evidence that genetic polymorphisms of certain NER genes can positively impact on the outcome of NB-UVB efficacy in the treatment of vitiligo by weakening DNA repair mechanisms leading to T cell death and so improved repigmentation rates.        3  Conflicts of interest None declared.  DR. E. HELEN KEMP Department of Human Metabolism University of Sheffield Sheffield S10 2RX U.K. Email ʹ e.h.kemp@sheffield.ac.uk    4  References 1 Alikhan A, Felsten LM, Daly M, Petronic-Rosic V. Vitiligo: a comprehensive overview Part I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up. J Am Acad Dermatol 2011; 65:473-91. 2 Mosenson JA, Zloza A, Klarquist J et al. HSP70i is a critical component of the immune response leading to vitiligo. Pigment Cell Melanoma Res 2012; 25:88-98.  3 van den Boorn JG, Konijnenberg D, Dellemijn TA et al. Autoimmune destruction of skin melanocytes by perilesional T cells from vitiligo patients. J Invest Dermatol 2009; 129:2220-32. 4 Westerhof W, Nieuweboer-Krobotova L. Treatment of vitiligo with UV-B radiation vs topical psoralen plus UV-A. Arch Dermatol 1997; 133:1525-28. 5 Njoo MD, Spuls PI, Bos JD et al. Nonsurgical repigmentation therapies in vitiligo. Meta-analysis of the literature. Arch Dermatol 1998; 134:1532-40. 6 Bhatnagar A, Kanwar AJ, Parsad D, De D. Psoralen and ultraviolet A and narrow-band ultraviolet B in inducing stability in vitiligo, assessed by vitiligo disease activity score: an open prospective comparative study. J Eur Acad Dermatol Venereol 2007; 21:1381-5. 7 Yones SS, Palmer RA, Garibaldinos TM, Hawk JL. Randomized double-blind trial of treatment of vitiligo: efficacy of psoralen-UV-A therapy vs narrowband-UV-B therapy. Arch Dermatol 2007; 143:578-84. 8 Wu CS, Yu CL, Lan CC, Yu HS. Narrow-band ultraviolet-B stimulates proliferation and migration of cultured melanocytes. Exp Dermatol 2004; 13:755-63. 5  9 Schwarz T, Schwarz A. DNA repair and cytokine responses. J Investig Dermatol Symp Proc 2009; 14:63-6. 10 Wei C, Jian Z, Wang L et al. Genetic variants of the APE1 gene and the risk of vitiligo in a Chinese population: a genotype-phenotype correlation study. Free Radic Biol Med 2013; 58:64-72. 11 Dai W, Zhou F-B, Wei C et al. A functional single-nucleotide polymorphism in the ERCC1 gene alters the efficiency of NB-UVB therapy in active vitiligo patients in a Chinese population. Br J Dermatol 2015; in press.   

The CC genotype of the ERCC1 C118T single-nucleotide polymorphism impacts positively on the efficacy of narrowband ultraviolet B therapy for vitiligo.

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The CC genotype of the ERCC1 C118T single-nucleotide polymorphism impacts positively on the efficacy of narrowband ultraviolet B therapy for vitiligo.

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