National Vitiligo Foundation
Grant Report - 1999

Genetics of vitiligo susceptibility

By identifying genes involved in vitiligo susceptibility, we can learn more about the cause of vitiligo. Depending on which genes are involved, what their normal function is, and what genetic changes are found in vitiligo patients, it may 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.

We have been using "case/control" studies to identify vitiligo susceptibility genes. These studies compare the variations of candidate genes present in patients vs. an unaffected control group. Large numbers of association tests must be performed for the reliable statistical results, and repeating the studies in different populations or ethnic groups is useful to confirm real associations. We are also using "family-based association", which requires DNA samples family members of the vitiligo patient. Families with one or more affected children can be analyzed, and the statistical tests 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.

Our goals for this research project last year were to expand our collection of vitiligo patient and family DNA samples, begin screening candidate susceptibility genes for association with vitiligo, and perform pilot studies of gene expression in melanocytes. We made good progress on our first goal, with the help of many members of the National Vitiligo Foundation and their families. We have now collected 500 samples in all, including 263 vitiligo patients and 237 unaffected family members. The patient group consists of 155 females and 107 males, with 202 Caucasians, 26 Hispanics, 10 African-Americans, 8 Indians, 6 other Asians, and 10 not reported. The average age of vitiligo onset in our patient group is 20 years old. As reported for other vitiligo patient groups, our group appears to have a higher incidence of thyroid disease and some other autoimmune conditions than the general population.

We have been collecting samples from affected and unaffected family members of vitiligo patients for the family-based association studies. We have obtained samples from 79 vitiligo patients without family members, 77 patients with only one or two first-degree relatives, and 48 patients with three or more relatives. We welcome additional participants regardless of family member participation and ethnic background, but we are especially interested in collecting family samples consisting of the patient, both parents, and at least one sibling, and we would like to increase the number of samples from non-Caucasian patients.

Our second goal was to begin case/control association studies of candidate vitiligo susceptibility genes. The testing of 26 candidate genes is nearly complete, including twelve genes important for melanocyte function and fourteen genes involved in regulating the immune system. A total of 45 genetic markers have been evaluated, 35 of which have proven to be informative. Based on our results so far, we have evidence that two of the melanocyte function genes and two of the immune system regulatory genes tested may be associated with vitiligo susceptibility. These genes are being studied further.

The third goal of these studies was to perform pilot studies of gene expression in melanocytes grown in culture from skin biopsies. Due to the difficulties in culturing adult human melanocytes, we are expanding this part of our research to include the identification of immune cells (T lymphocytes) in the blood that home to the skin of vitiligo patients. We will begin comparing patterns of gene expression in melanocytes and lymphocytes from patients and unaffected individuals this year. The aim of these experiments is to identify genes that are expressed abnormally in patient cells as compared to control cells using molecular biology techniques that do not rely on previous knowledge about melanocyte function.