New gene that affects clearance of hepatitis C virus discovered

New gene that affects clearance of hepatitis C virus discovered

Researchers at the National Cancer Institute (NCI), along with investigators from other institutions, have made further progress on hepatitis C virus infection. In their studies, they found that the clearance of hepatitis C virus is genetically determined and that  there is also a gene variant,  called interferon gamma 4 (IFNL4), which predicts treatment response. The study results were published in Nature Genetics.

Hepatitis C is a major health problem that affects approximately 3% of the world population. Hepatitis C is one of the most serious infections because of the risk of liver cirrhosis and hepatocellular carcinoma. It seems that up to 80% of those infected with the virus C fail to eliminate the virus and progresses to chronic hepatitis. Of these, about 5% develop liver cancer. Even though recently there have been made advances in virus C infection treatment, what is remarkable is that not all patients respond in the same way to treatment. There is a difference between African patients and European or Asian patients regarding treatment response.

Studies so far have shown that there is a genetic component that determines the response to virus infection C. Using genome-wide association studies (GWAS) there has been shown that there are genetic markers located on chromosome 9 (near the interferon gene, IFNL3) that influence response to treatment.

To discover the new gene, the researchers used a different technique involving RNA sequencing on human liver cells that were infected with virus C. Co-lead investigator Ludmila Prokunina-Olsson, Ph.D., of the Laboratory of Translational Genomics in NCI’s Division of Cancer Epidemiology and Genetics (DCEG), was excited about this approach and said that it is possible to find other genes with RNA sequencing.

It seems that IFNL4 region has two variants. One of them, called deltaG, is the deletion variant and it seems that it is more common in patients from Africa, patients that do not respond to treatment so well as those from Europe or Asia. The deletion variant refers to an abnormality in DNA structure leading to the formation of a protein called IFNL4 protein,  protein that is associated with a poorer clearance and poorer response to treatment. However, the mechanism by which protein IFNL4 interfere with the clearance of hepatitis C virus is unknown.

NCI’s Thomas R. O’Brien, MD, Infections and Immunoepidemiology Branch, DCEG, said that these findings  may lead in the future to personalized medicine. In other words, it is a step forward to more effective therapies. He also said that INFL4 protein may be a new therapeutic target  not only for C virus infection treatment but also for other diseases.