Spotlight on Research 2010

September 2010 (historical)

Genetic Discoveries Hold Clues to Vitiligo and Malignant Melanoma

Research supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) has uncovered variations in at least 13 genes associated with vitiligo, a chronic disorder in which destruction of pigment-producing cells, called melanocytes, results in irregular white patches of skin and hair. The findings, say researchers, provide new clues to understanding the disease, which affects approximately 0.5 to 1 percent of the world’s population. But perhaps more importantly, it provides clues into another disease, which is opposite of vitiligo — malignant melanoma. The most deadly form of skin cancer, malignant melanoma occurs when the melanocytes grow unchecked. The study appears in the New England Journal of Medicine.

The genetic variations were discovered through a genome-wide association study, which compared the genetic makeup of 1,514 people with vitiligo to that of 2,318 control subjects without the disease. Data for control subjects were obtained from dbGaP, a database developed by the National Library of Medicine’s National Center for Biotechnology Information, to archive and distribute data for genome-wide association studies.

In the study, researchers led by Richard Spritz, M.D., director of the Human Medical Genetics Program at the University of Colorado School of Medicine, tested over 600,000 single-nucleotide polymorphisms — tiny variants in the genes' DNA sequence — for any association with vitiligo. Not surprisingly, most of the genes they identified were associated with the immune system, confirming the belief that vitiligo is an autoimmune disease, a disease that occurs when the immune system attacks components of the body.

Perhaps the most important finding is the association with the TYR genetic locus, which encodes tyrosinase, an enzyme required for the production of skin pigment. However, the researchers suspect that the role of tyrosinase in vitiligo is not only involved in making pigment, but, in addition, is involved in directing the immune system to attack the pigment-making melanocytes. When the process is working properly, tyrosinase recognition may help the immune system search out and destroy cells that could proliferate and form melanoma tumors. If the process is overactive, however, it might lead to vitiligo.

While the researchers set out to learn more about vitiligo, they say the more immediate application of their findings may be for melanoma. By finding drugs that regulate immune recognition of melanocytes, they may be able to effectively treat melanoma and vitiligo.

The other good news for people with vitiligo is that since many of the genes identified are involved in the immune system, it may be that drugs used for — and being developed for — other autoimmune diseases may be beneficial for vitiligo as well.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. Department of Health and Human Services’ National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at


Jin Y, Birlea SA, Fain PR, Gowan K, Riccardi SL, Holland PJ, Mailloux CM, Sufit AJ, Hutton SM, Amadi-Myers A, Bennett DC, Wallace MR, McCormack WT, Kemp EH, Gawkrodger DJ, Weetman AP, Picardo M, Leone G, Taïeb A, Jouary T, Ezzedine K, van Geel N, Lambert J, Overbeck A, Spritz RA. Variant of TYR and autoimmunity susceptibility loci in generalized vitiligo. N Engl J Med. 2010 May 6; 362(18):1686-97.