Vitiligo: New genetic knowledge could lead to new treatments

National report - New understanding has led to new approaches in the search for the genetic origins of generalized vitiligo, says a leading researcher in the field.

"I feel strongly that it's important to be precise in defining vitiligo," says Richard A. Spritz, M.D., professor and director of the Human Medical Genetics Program at the University of Colorado Health Sciences Center. "Unfortunately, that historically hasn't always been the case in the field of vitiligo."

Generalized vitiligo

He says that vitiligo is what geneticists refer to as a complex trait.

Additionally, he says, "There's now overwhelming evidence that in the great majority of cases, generalized vitiligo is an autoimmune disease. It's time to stop talking about 'if' it's an autoimmune disease and accept that it is, and to give less credence to a number of alternative hypotheses that have been suggested with little or no evidence to support them."

Family studies

In keeping with this perspective, Dr. Spritz's lab sent an extensive questionnaire to approximately 10,000 vitiligo patients in the United States and the United Kingdom and received approximately 4,000 responses. These responses gave researchers a clearer picture of various aspects of vitiligo, including average age of onset, extent of skin involvement and how often it occurs in close relatives, he says. From there, researchers were able to identify multiplex families - families with two or more people who have vitiligo - who might take part in their studies.

Dr. Spritz says, "One can only perform genetics linkage analysis in the context of multiplex families. What one is asking is, if there are two people in a family who have vitiligo, what in the genome do they tend to share as a group? What do they share more frequently than they should by chance?"

Based on study responses, researchers to date have performed DNA analysis on approximately 650 individuals in 200 families.

"First," Dr. Spritz says, "we looked across the entire genome for indications of where (mutated) genes might be. The answer we got in one particular very large family was there seemed to be an important gene on chromosome 1, and we believe we've found what probably is that gene - FOXD3. However, that gene appears to only play a key role just in that one very large family, which appears to be different from all families we've studied."

In that family, he explains, vitiligo tends to behave as if it is caused by only one gene (Alkhateeb A, Fain PR, Spritz RA. J Invest Dermatol 2005;125:388-391.).