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 turns 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 the 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.

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Multiple sclerosis (MS) afflicts the central nervous system, causing unpredictable and varying symptoms that differ from person to person. About one in 700 people in the United States is affected by the disease. Although there is currently no cure for MS, there are treatments that can slow the progression of the disease and enhance the quality of life for people who have this condition.

Researchers have identified several genetic variants in the HLA region of the genome –an area containing many genes involved in immune system function – that seem to affect MS symptoms, disease severity, and response to treatment. One of these variants is in the HLA-DRB1 gene. Known as HLA-DRB1*1501, this variant is associated with increased risk for MS, though exactly how it is involved in development of the disease is unclear.

In a report published online today in the journal Archives of Neurology, a team of researchers led by Drs. Madeleine Sombekke and Chris Polman of Vrije University in Amsterdam uncovered a clue which may elucidate the connection between the HLA-DRB1*1501 variant and multiple sclerosis. They analyzed *1501 and other genetic variants in 150 Dutch individuals with multiple sclerosis to see if any of the SNPs were associated with variation in brain and spinal cord lesions.

One SNP in particular, rs3135388 (used as a proxy for HLA-DRB1*1501), was associated with spinal cord lesions. People carrying at least one copy of the A version of rs3135388 had significantly more spinal lesions and had more segments of the spinal cord affected than people with two copies of the G version.

(23andMe Complete Edition customers can check their data for rs3135388 using the Browse Raw Data feature.  This SNP is also part of the Multiple Sclerosis Research Report available to Health and Complete Edition customers.)

MS is believed to be an autoimmune disorder – wherein the immune system attacks the body’s own cells rather than foreign invaders – and so it makes sense that genetic variants in immune system genes would influence the course of the disease and its clinical features. HLA genes, in particular, encode proteins that contribute to self vs. non-self immune recognition. Previous studies have proposed a link between HLA-DRB1*1501 and disease severity. Since lesions on the spinal cord are often used to diagnose MS and the degree of disability, Sombekke’s team suggests that the association of HLA-DRB1*1501 with spinal cord lesions might help explain its relationship with severity of the disease.

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

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The most common type of arthritis, osteoarthritis, occurs due to accumulated wear and tear – welcome to old age! – or from repetitive movements or injury.  Rheumatoid arthritis, on the other hand, is caused by an autoimmune attack on the lining of the joints, resulting in stiffness, muscle aches, and general fatigue. Approximately two million people in the U.S. suffer from rheumatoid arthritis, and although women are affected more often than men, men tend to have more severe symptoms.

Research has identified a number of genetic factors that contribute to one’s risk of developing rheumatoid arthritis, and new studies continue to reveal more genes that seem to be involved in this complex disease. In a report published this week in Nature Genetics, a team led by Soumya Raychaudhuri and Robert Plenge of Brigham and Women’s Hospital in Boston describe three new genetic associations with rheumatoid arthritis risk.

Using a computational algorithm that incorporates information from the scientific literature, Raychaudhuri and his colleagues identified 22 candidate SNPs that have a large number of connections to previously validated genetic risk factors for rheumatoid arthritis. When they tested these SNPs in a set of almost 8,000 Caucasians with rheumatoid arthritis and 12,000 controls, seven emerged as highly significant associations. After combining this study population with that from a previous study – for a total of more than 11,000 individuals with rheumatoid arthritis and 22,000 without  – three of the variants rose to the top.

All three variants are in genes not previously linked to rheumatoid arthritis. Each copy of a C at rs1980422 and each copy of a G  at rs11586238 increased an individual’s odds of developing the condition by 1.13 times. Similarly, each copy of a C at rs548234 increased the odds of rheumatoid arthritis by 1.11 times.

(23andMe customers can see their data for the SNPs currently covered by 23andMe’s service by using the Browse Raw Data feature. 23andMe currently does not report on rs11586238, but does report on a SNP that acts as a perfect proxy for it, rs12405671. The A version of rs12405671 corresponds to the G version of rs11586238.)

These three SNPs are located near genes involved in the immune response, and, in some cases, near genetic variations that have been associated with other autoimmune disorders, such as Crohn’s disease and type 1 diabetes. Although a detailed, cohesive picture of the causes underlying rheumatoid arthritis remains elusive, each new association discovered by researchers contributes to our understanding of the biological players involved in this autoimmune disease.

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

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Stanford researchers are also studying narcoleptic dogs.

Ten years ago, the daytime drowsiness, irregular nighttime sleep and sudden loss of muscle tone and strength associated with narcolepsy were traced to the lack of a protein called hypocretin.  Further research showed that narcoleptics’ brains are missing the cells that produce this important wakefulness-promoting hormone.

Scientists didn’t know exactly why the hypocretin-secreting cells were missing in the brains of narcoleptics, but they did have a hunch.  More than 90% of people with narcolepsy carry a particular variation in an immune molecule that helps the body distinguish itself from foreign invaders like bacteria and viruses.  This led some researchers to suggest that narcolepsy is an autoimmune disease.

But 20% of people without narcolepsy also carry the immune molecule variation, indicating that there must be other genetic and/or environmental factors at work.  Now a new report, published online yesterday in the journal Nature Genetics, adds more evidence to the autoimmune theory of narcolepsy by showing that variations in another immune-related gene are also associated with this condition that affects about one out of every 2,000 people.

In a sample of approximately 1,800 people (about 800 with narcolepsy and 1,000 without), all with European ancestry and all carrying the immune molecule variation found in most narcoleptics, researchers led by Stanford’s Emmanuel Mignot found that variations in the TRA@ gene, which encodes a receptor found on specialized immune cells called T cells, are associated with narcolepsy.

The scientists confirmed their findings in a second group of Caucasians, as well as in Asian (Japanese and Korean) and African American samples, although the size of the African American sample was too small for statistically significant data to be gathered.

(23andMe customers can get more information on the identified variations at the end of this post.)

In a statement, Mignot said that he thinks it is likely that the T cell receptor variations identified in this study and the immune molecule variation previously found in narcoleptics interact to kill hypocretin-secreting cells, but that more research will be needed to understand exactly how this happens.  He went on to say that once these interactions are understood, scientists might be able to identify people at risk for narcolepsy and perhaps stop development of the disease.

In addition to shedding light on the biology of narcolepsy, the authors of the study think their findings will help researchers studying other autoimmune diseases such as multiple sclerosis and type 1 diabetes.

“I’m sure immunologists are going to be very excited.  If we can work out what happens specifically in patients with narcolepsy, we’ll be able to better understand the role of T cells in other autoimmune diseases that are more complicated and difficult to detect,” Mignot said in a statement.

• The strongest link with narcolepsy was found with rs1154155, but 23andMe cannot currently provide data for this SNP.  Instead, customers can use the Browse Raw Data feature to look at a closely related SNP also described in the paper:  Each copy of the G version of rs12587781 increased the odds of narcolepsy by 1.79 times in Europeans and 1.34 times in Asians.  The G version of rs12587781 showed a trend towards increased odds of narcolepsy for African Americans, but the results were not statistically significant.

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