Vitiligo Susceptibility Genes Associated With Immune Regulation Identified Interview with:

Richard Spritz, Director of the Human Medical Genetics and Genomics Program at the University of Colorado School Medicine, led a recent study that explored the genetic links between eye color and serious skin conditions like vitiligo and melanoma. (Marla R. Keown/Aurora Sentinel)

Dr. Richard Spritz,

Richard A. Spritz, M.D.
Professor and Director,
Human Medical Genetics and Genomics Program
University of Colorado School of Medicine.
Aurora, CO 80045 USA What is the background for this study? What are the main findings?

Response: Vitiligo is an autoimmune disease in which depigmented skin results from destruction of skin melanocytes, with strong epidemiologic association with several other autoimmune diseases that include autoimmune thyroid disease, type 1 diabetes, rheumatoid arthritis, pernicious anemia, systemic lupus erythematosus, and Addison’s disease.

In previous genetic linkage and genome-wide association studies (GWAS) of vitiligo patients of European-derived white ancestry (EUR), we identified 27 vitiligo susceptibility loci. In the present study, we carried out a third GWAS of vitiligo in EUR subjects. The combined analysis, with almost 5,000 vitiligo cases and 40,000 non-vitiligo controls, identified a total 23 new confirmed vitiligo loci, as well as seven with suggestive significance. What should readers take away from your report?

Response: Most of the identified vitiligo susceptibility loci encode immune regulators, apoptotic regulators, and melanocyte regulators and antigens, highlighting a complex web of pathways that represent a general circuit from antigenic triggering, immune signal propagation and amplification, to target recognition and destruction by autoreactive T cells. Many of the immunoregulatory genes have also been identified in genetic studies of other autoimmune diseases, underscoring the basis for epidemiologic association of these related diseases. Most of the melanocyte antigens and regulators have also been identified in genetic studies of melanoma, but with opposite genetic effects, suggesting that vitiligo might represent a dysregulated mechanism of immune-surveillance for nascent melanomas. Fine-mapping suggests that most causal variants at the identified vitiligo loci are regulatory in nature. The findings of this study suggest a number of potential new drug targets for treatment or prevention of vitiligo and other autoimmune diseases. What recommendations do you have for future research as a result of this study?

Response: Future research will be aimed at identifying the specific causal variation at the identified vitiligo susceptibility genes, understanding the functional effects of these variants, devising approaches to using these and other variants to predict vitiligo risk, and developing personalized medicine approaches to target vitiligo treatment based on specific genetic risk. Thank you for your contribution to the community.

Ying Jin, Genevieve Andersen, Daniel Yorgov, Tracey M Ferrara, Songtao Ben, Kelly M Brownson, Paulene J Holland, Stanca A Birlea, Janet Siebert, Anke Hartmann, Anne Lienert, Nanja van Geel, Jo Lambert, Rosalie M Luiten, Albert Wolkerstorfer, J P Wietze van der Veen, Dorothy C Bennett, Alain Taïeb, Khaled Ezzedine, E Helen Kemp, David J Gawkrodger, Anthony P Weetman, Sulev Kõks, Ele Prans, Külli Kingo, Maire Karelson, Margaret R Wallace, Wayne T McCormack, Andreas Overbeck, Silvia Moretti, Roberta Colucci, Mauro Picardo, Nanette B Silverberg, Mats Olsson, Yan Valle, Igor Korobko, Markus Böhm, Henry W Lim, Iltefat Hamzavi, Li Zhou, Qing-Sheng Mi, Pamela R Fain, Stephanie A Santorico, Richard A Spritz. Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants. Nature Genetics, 2016; DOI: 10.1038/ng.3680

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Last Updated on October 13, 2016 by Marie Benz MD FAAD