Genetic Research

There is a genetic component to alopecia areata, which means that heredity plays a role. In one out of five persons with alopecia areata, someone else in the family also has it. Those who develop alopecia areata for the first time after the age of thirty are less likely to have another family member with it. Those who develop their first patch of alopecia areata before the age of thirty are more likely to have other family members with it. Because of these truths, NAAF has focused a lot of its research into investigating the genetics of alopecia areata in hopes of determining what role genetics truly play in alopecia areata, including uncovering the mysteries of who is most susceptible and why.

Foundation of Genetic Research and Alopecia Areata

In the 1990’s, the scientific community as a whole made great strides in being able to answer questions about genetics. The Human Genome Project at the National Institutes of Health brought us access to a wealth of information. And there were tremendous advances in looking at single-gene disorders like cystic fibrosis. In single-gene disorders whoever gets the gene also gets the disease.

But alopecia areata is a polygenic disease, that is, it involves multiple genes and is therefore very complex. It is a bit like the many shades of gray; different genes in different combinations all play a role in this disease and researchers are working to untangle the web of these genetic relationships. This is much harder than looking at single genes. Prior to the completion of the Human Genome Project we were not even able to look at five or more genes in combination. The Human Genome Project and new gene technology has given geneticists the tools to step back and look globally at all the genes and identify hot spots.

As a result, the research studies that are now being designed for alopecia areata are focusing on large families, or what are called multiplex pedigrees, in which three or more people all have symptoms of alopecia areata. In preliminary studies we have found that alopecia areata has genes in common with other autoimmune diseases including psoriasis and arthritis.

Genetic Analysis

Angela Christiano, Ph.D. is one of several people involved in a comprehensive genetic analysis of people with alopecia areata. She is doing a genome-wide scan, looking at all the genes that comprise human beings, in a collection of families that have many family members with alopecia areata. She hopes these studies will lead to the identification of the many genes that make people more susceptible to alopecia areata. Then we can begin to understand how these genes interact with each other and ultimately how they may lead to the cause or the cure of alopecia areata. The susceptibility genes are probably affecting individual components of the hair follicle. They may affect one component or they may affect more than one component, and so we have to study the individual components sometimes to pin down what the susceptibility genes are doing.

NAAF-funded research has also identified two specific chromosomes that may be linked to an individual’s susceptibility to alopecia areata. For many years, Angela Christiano, Ph.D. has conducted genome-wide searches for linkage from sibling pairs enrolled in the National Alopecia Areata Registry. To maximize the outcome of her gene-mapping, she has focused her initial efforts on the pedigrees of individuals from families where three or more members are affected with alopecia areata. She has already completed 22 pedigrees, and she has started to see spikes in the areas of certain chromosomes.

The exciting news is that the locus on chromosome 10 identified in the analysis of alopecia areata in the first panel of families overlaps the locus on chromosome 10 obtained in the second and third panel of families. And the locus identified on chromosome 6 in the second and third panels of pedigrees overlaps with one of the loci identified in a genome wide scan done previously on the mouse model for alopecia areata.

These results represent the first significant evidence of genetic susceptibility for alopecia areata in humans as identified in a whole genome analysis! In particular, due to the fact that certain chromosomes appear among the top scores for at least three of the four tests performed, these results pinpoint regions on various chromosomes that might harbor alopecia areata susceptibility genes.

Mouse Model Genetics

John Sundberg, Ph.D., DVM is doing genetics on the mouse animal model for alopecia areata some more related work. He's been studying the alopecia areata mouse model-a special inbred type of mouse with alopecia areata-and he has noted that even in this mouse it appears that there are many different genes responsible for causing the disease. The genetics in these inbred mice have not even been sorted out yet, and it's very likely that the situation in human beings is much more complicated because we are a very outbred type of mammal.

Susceptibility Genes and White Blood Cells

Nazilia Barahmani, Ph.D. and her colleagues have reported a very interesting observation. A man who had leukemia received a bone marrow transplant from his brother as a part of his leukemia treatment. It just so happened that the brother had alopecia areata. It also happened, by coincidence, that these brothers had the exact same HLA immunity genes, including one gene that has already been identified as a susceptibility gene for alopecia areata. Now the patient did very well-he had no evidence of rejection-and so his anti-injection medications were stopped. At that point he developed alopecia areata just like his brother had. This suggests that the white blood cells of a person with alopecia areata can cause alopecia areata in a genetically related person with the right susceptibility.