SNPwatch: New Variants Associated With Lupus in Europeans and Asians

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Lupus, which means “wolf” in Latin, gets its name from the skin manifestations sometimes seen in the disease. A physician in the 13th century thought they looked like wolf bites.

In autoimmune disorders, the immune system — which normally protects us from harmful, foreign substances — goes into overdrive and starts attacking the body’s own cells, causing inflammation and organ damage.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic, widespread inflammation that can result in arthritis, fever, skin rashes, muscle aches, seizures and fatigue, among other symptoms. Some symptoms can even be life-threatening. Between one and seven out of every 10,000 people is affected by SLE. The disease affects women nine times more frequently than men, and tends to be more prevalent and severe in people of non-European descent. The exact causes of SLE are unknown and there is currently no cure.

For several decades now, researchers have probed the genetic underpinnings of this mysterious disease. Two studies published this week in Nature Genetics identify new genetic variants associated with SLE in European and Asian populations.

In the first study, a team led by Vesela Gateva and Robert Graham of Genentech identified ten novel genetic variants associated with SLE in a European group consisting of more than 3,000 people with the disease and 10,000 people without SLE. Half of these variants were previously associated with other autoimmune diseases, but this is the first time they have been associated with SLE. In addition, the researchers confirmed nine variants previously linked to SLE in other studies.

Of the previously reported autoimmune variants, Gateva and colleagues note that the A version of the variant is also a known risk variant for age-related macular degeneration, seems to be protective against SLE, although additional research will be needed to confirm this effect.

One of the SNPs not previously associated with SLE or any other autoimmune disease,  is in the gene that encodes TNIP1.  The TNIP1 protein is known to interact with TNFAIP3, a protein that genetic studies have previously linked to rheumatoid arthritis, psoriasis and type 1 diabetes — all autoimmune disorders — suggesting that the TNIP1-TNFAIP3 association may play a general role in autoimmunity.

In the second study, Jian-Wen Han and Xue-Jun Zhang’s team from Anhui Medical University in China identified 21 genetic variants associated with SLE in more than 4,000 Chinese individuals with the disease and 8,200 individuals without autoimmune disorders. About half of the associations confirmed previous reports in European populations, and half represented novel findings.

Interestingly, one of the new variants they identified is also in the TNIP1 gene. Here, each copy of a T increased odds of SLE by about 1.24 times. Many other SNPs associated with SLE in the Chinese study were located in or near genes involved in immune response.

The TNIP1-TNFAIP3 connection and association of variants known to be linked to other autoimmune diseases add to growing evidence that common genetic factors contribute to autoimmunity. These findings may help pave the way for novel therapeutics for autoimmune disease that exploit this shared genetic basis.






  • Susan

    How can a participant find out their personal SNP or version?

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