SNPwatch: Genetic Variations Associated with Autoimmune Form of Hair Loss, Alopecia Areata

Alopecia areata is a form of hair loss many people are unfamiliar with, although the condition affects more than five million people in the United States.  Unlike male (or, more rarely, female) pattern baldness, which is thought to be caused by hormones, alopecia areata results from an autoimmune attack on hair follicles.  It can lead to the loss of hair on the scalp and elsewhere on the body.  Men and women are affected equally.

As is the case for most autoimmune diseases, whether or not a person is affected by alopecia areata is at least partially determined by genetics.  But finding the genes responsible for the condition has so far not been very successful.  The first genome-wide association study of alopecia areata, however, has yielded a bumper crop of genetic variants associated with the condition.  These results, published online today in the journal Nature, not only shed light on biology behind alopecia areata, but may also guide the development of new treatments.

“This research is very exciting as alopecia areata affects a huge number of people worldwide, and there are very few treatments for it —resulting in an enormous unmet medical need,” said Vicki Kalabokes, president and CEO of the National Alopecia Areata Foundation, in a statement.

A team of researchers led by Angela Christiano of Columbia University analyzed the DNA of 1,054 people with alopecia areata and 3,278 controls, all of European ancestry.  They found 16 blocks of variation that showed significant association with risk for the condition.  Some of the variations the researchers found were, not surprisingly given the autoimmune nature of alopecia areata, in genes involved in the immune system.  But others were in genes turned on in the hair follicles themselves.

(The details of the strongest SNP from each of the 16 blocks are in a table at end of the post.)

One of the hair follicle genes identified in the study was ULBP3.  This gene encodes a protein that signals to the immune system that a cell is under stress or in danger and should be destroyed for the good of the rest of the body.  When the researchers looked at hair follicles under a microscope, they found that follicles from people with alopecia areata had higher than normal levels of ULBP3.  They also found that many of the immune cells attacking the follicles expressed NKG2D, the receptor that recognizes and binds to the protein.

More research will be needed to confirm these findings, but Christiano’s team suggests that in genetically susceptible individuals, increased ULBP3 acts as the initiating factor for the autoimmune response seen in alopecia areata.  If this is true, it could open up new avenues of treatment.

Because the symptoms of alopecia areata resemble those of psoriasis, another autoimmune disorder, doctors have tried treating the hair loss condition with the same treatments used for psoriasis.  But they have seen little success.  This new study shows why – very few of the genes involved in alopecia areata are also linked to psoriasis, suggesting that the diseases don’t share much similarity at the molecular level.

Many of the alopecia areata genes, however, have been linked to other autoimmune diseases, including type 1 diabetes, rheumatoid arthritis and celiac disease.  All of these diseases have also been connected to immune cells expressing the NKG2D receptor.  In a statement, Christiano explained that since drugs targeting this receptor are already in development for these other autoimmune disease, researchers may soon be able to test these same medicines in clinical trials for alopecia areata.

“Finally, we have the possibility of developing drugs that specifically target the mechanism behind the disease,” said Christiano.

SNPRisk VersionIncrease in Odds per Risk Copy T1.44 C1.32 T1.34 T1.65 C1.52 C1.32 A1.30 C1.41 G1.34 A1.32 G2.21 A1.95 C1.88 A1.70 G1.57 A1.33