Genes Newly Linked to Skin Disease May Lead to Better Understanding of Lupus

Researchers identified 23 genes associated with a predisposition for vitiligo, an autoimmune disease characterized by patches of skin and hair that lack pigmentation. Their discovery may lead to a better understanding of other autoimmune conditions, such as lupus.

The study, “Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants,” was published in the journal Nature Genetics.

Richard Spritz, MD, a professor at the University of Colorado School of Medicine and director of the Human Medical Genetics and Genomics Program, has spent the past decade trying to identify the causes of vitiligo, a disease that gives rise to patches of white skin and hair.

Working with colleagues worldwide, he conducted genome-wide association studies into 4,680 people of European ancestry with vitiligo and 39,586 controls. The research team identified 23 new loci — or a gene’s position in a chromosome — that are significantly associated with vitiligo, and seven suggestive loci. These findings provide a framework for the genetic and biological mechanisms of vitiligo, a disease that is epidemiologically associated with several other autoimmune diseases, including lupus, adult-onset type 1 diabetes, and rheumatoid arthritis. For this reason, it may lead to progress in treating those diseases as well.

“This study doubles the number of known genes involved in risk for vitiligo,” Spritz said in a news release.

Most of the genes identified were linked to immune regulators, as well as to regulators of apoptosis (programmed cell death). Several melanocyte regulators were also found in these loci. Melanocytes are cells that produce melanin, the pigment primarily responsible for skin color, which are destroyed in vitiligo. Many genes involved in melanocyte development have also been implicated in melanoma, an aggressive form of skin cancer, and these two diseases are also thought to be linked.

“One of the purposes of the genome project was to give us the tools to do more complicated disease analysis,” Spritz said. “What’s emerging in general for complex diseases is that it is changes in gene regulation rather than gene structure that are causes.”

Researchers are now using DNA sequencing and genetic studies to identify vitiligo-causing mutations in these genes. Their study will involve a large number of patients, of diverse ethnic backgrounds, with the disease.

“Like a jigsaw puzzle, the pieces of the vitiligo pathogenome are thus beginning to fit together, revealing a complex network of immunoregulatory proteins, apoptotic regulators, and melanocyte components that mediate both autoimmune targeting of melanocytes in vitiligo and susceptibility to melanoma,” the researchers wrote.