Advanced cirrhosis of the liver in an alcoholic patient. Source: Ed Uthman

Regeneron Pharmaceuticals claims to have found individuals carrying a gene mutation that grants them a level of immunity to cirrhosis. The research, published in the New England Journal of Medicine today, identified a gene that correlated with as much as a 73% reduced risk of the condition due to drinking and as much as a 30% reduction in non-drinkers.

Cirrhosis, also known as fatty liver disease, is a condition that has been becoming more prevalent as a result of increased levels of alcoholism and overeating. At present, it is thought that as many as 1 in 4 residents of the USA suffer from the condition.

The increasing number of patients has led many drug developers to investigate new avenues of treating cirrhosis of the liver, helping patients and opening up new revenue streams. It was to this end that Regeneron Pharmaceuticals, a biotech company based in the US, chose to explore their DNA repository for people who demonstrated cirrhosis-resistance or immunity. Through a partnership with Geisinger Health System, Regeneron have built a database that grants them access to the genetic information of thousands of volunteers.

The study involved examining the electronic health records, blood serum measurements, and exome sequence data of 46,544 participants to identify loci that were associated with levels of alanine aminotransferase and aspartate aminotransferase. Any variants that were identified in the first round of analysis were subsequently verified in three other cohorts that totalled 12,527 individuals. Once this analysis was complete, the variants that remained were evaluated for their association with liver disease in a further two independent cohorts (37,173 individuals in total) and 2391 human liver samples.

This analysis led the team to a gene called HSD17B13. Their results demonstrated that individuals who did not carry a working copy of the gene were at a considerably lower risk of developing cirrhosis. In cases of non-alcoholic liver disease, heterozygotes were at a 17% reduced risk and homozygotes saw a 30% reduction in risk. When considering alcoholic cirrhosis, the risk was reduced by 42% and 73% respectively, and for non-alcoholic cirrhosis, it was a reduction of 26% and 49% respectively.

The study did not identify how an inactivation of the HSD17B13 gene created this protective effect, but it still presents an opportunity for Regeneron to develop novel cirrhosis medicines. If a drug can be produced that can silence or repress the activity of the gene, then it may be possible to mimic the effect seen in this study.  To better enable this development process, Regeneron is hoping to partner with Alnylam Pharmaceuticals, who specialise in gene-silencing medications.