Vitiligo is a pigment disorder of the skin, which is seen on patients as de-pigmented areas of the skin that may gradually enlarge. Vitiligo is a common condition, affecting about 1% of all racial groups worldwide, and predisposes affected persons to skin damage by sunburn. Vitiligo is also associated with an increased risk for other autoimmune diseases, such as thyroid conditions. The current treatments for vitiligo are difficult, expensive, and often disappointing. The cause of vitiligo is unknown, but is thought to involve both genetic and environmental factors. Vitiligo sometimes runs in families, and one study found that 20% of the relatives of vitiligo patients also have vitiligo, with the highest risks for children and siblings of patients. This suggests that some people are born with genes that make them more susceptible to developing vitiligo. These genes may be important for the normal function of the pigment-producing cells in the skin (melanocytes) and/or in cells of the immune system (lymphocytes). Environmental factors, such as traumatic skin injury, sunburn, or stress, appear to influence whether or not an individual with those “susceptibility genes” will develop vitiligo during their lifetime.

By identifying disease susceptibility genes, we can learn more about the cause of vitiligo. Depending on which genes are involved, what their normal functions are, and what genetic changes are found in vitiligo patients, it might be possible to design new treatments based on understanding those genes. Knowing which genes are important may also allow genetic testing for individuals that might be predisposed to having vitiligo, so that environmental risk factors can be more carefully avoided. Theoretically, it is possible that future advances in gene therapy might also help susceptible or affected persons.

At the University of Florida, under the direction of Drs. Margaret “Peggy” Wallace and Wayne T. McCormack, we are using “case/control association” to try to identify vitiligo susceptibility genes. Case/control studies compare the variations of potential vitiligo susceptibility genes that are present in patients compared to an unaffected control group. A gene variant or change will be considered to be associated with vitiligo susceptibility when it is found more often in vitiligo patients than in controls. Large numbers of association tests must be performed for the most reliable statistical results, and repeating the studies in different populations or ethnic groups is extremely useful to confirm real associations. We are also using “family-based association,” which requires DNA samples from family members of the vitiligo patient. Families with one or more affected children can be analyzed, and statistical tests can help determine whether a particular genetic change in a vitiligo susceptibility gene is passed from parents to affected children more frequently than expected due to random chance. The advantages of family-based association studies include the use of families with any number of affected children, and the combining of information from multiple ethnic groups and/or geographical populations.

The goal of these studies is to test the hypothesis that susceptibility to vitiligo is a complex genetic trait involving a number of genes. Some of the genes we are investigating are known to be expressed in melanocytes, which may predispose them to self-destruction and/or target them for autoimmune destruction. Other genes we are investigating are known to be involved in the immune system, which may contribute to the autoimmune response in vitiligo patients. The long-term goals of this research include determining whether “at risk” individuals can be identified in families with a history of vitiligo, which might influence the choice of strategies for treatment or prevention of vitiligo, and whether novel therapies that might prevent or ameliorate vitiligo can be devised based on an understanding of vitiligo pathogenesis and genetic susceptibility. In addition, these studies may contribute to an overall understanding of genetic susceptibility to autoimmune disease, given the possible association of vitiligo with other autoimmune endocrinopathies.