SNPwatch: Researchers Link Variations In Immune System Genes with Primary Biliary Cirrhosis

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.

A new report, published online today in the New England Journal of Medicine, shows that several variations in genes related to the immune system are associated with primary biliary cirrhosis (PBC), adding support to the theory that the condition is caused by an autoimmune reaction in which the body’s own defense system turns against itself.

PBC is a chronic disease that slowly destroys bile ducts within the liver.  Inflammation causes bile to remain in the liver, leading to gradual injury and eventual scarring. People with PBC may remain symptom-free for many years after diagnosis, but cirrhosis can eventually lead to life-threatening complications.  Women account for about 90 percent of PBC cases — up to one in 1,000 over 40 are affected by the condition.  Studies have shown that genes influence the risk of developing PBC, but so far only a few genetic variations have been linked to the disease.

Gideon Hirschfield and colleagues analyzed the DNA from a total of 1,031 people with PBC and 2,713 controls, all with European ancestry.  They found associations between several variations in the HLA region of the genome and the condition.  The genes in this region of DNA encode proteins that help the body distinguish between its own tissues and foreign invaders like viruses and bacteria. The strongest association was with rs2856683: each G increased the odds of PBC by 1.75 times compared to having two Ts.

The researchers also identified variations in the IL12A and IL12RB2 genes, which encode proteins involved in immune system signaling.  Each G at rs6441286 in the IL12A gene increased the odds of PBC by 1.54 times.   In the IL12RB2 gene, each A at rs3790567 increased the odds of PBC by 1.51 times.

Several other variations, many also in immune system-related genes, were also associated with PBC, though not as strongly as those detailed above.

According to the authors of the study, their findings will not only help scientists better understand the causes of PBC, but may also aid in the search for treatments.  For instance, the authors suggest drugs that modify signaling by interleukin-12α and its receptor (encoded by the IL12A and IL12RB2 genes, respectively) might be beneficial for patients with PBC.