Genetic clue for ridding the body of hepatitis C

September 17, 8:57 AMScience News ExaminerMeg Marquardt

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Electron microscope of HCV. Credit: PhD Dre (source)

Johns Hopkins researchers have found a unique variable in those who are able to defeat Hepatitis C virus (HCV), which can cause a vicious infection in  liver, without the aid of medication.  As over 4 million Americans are infected with that disease, understanding this quirk of genetics may lead to better therapies and eventually a vaccin

"If we knew why some people got rid of the disease on their own, then maybe we could figure out ways to help other people who didn't," says David Thomas, M.D., professor of medicine and director of infectious diseases at Johns Hopkins. "Or maybe even help prevent infections entirely."

An earlier study had found that a small portion of DNA, known as a single-nucleotide polymorphism, or SNP, was involved with a patient's ability to defeat HCV.  Those with the C/C variant of the SNP had a more successful response to HCV treatment. The SNP is found near the poorly-understood IL28B gene, which is thought to be involved with immune response.

So the Hopkins-and-National-Institutes-of-Health-led team wondered if the C/C variation—as opposed to the C/T or T/T alternatives—also played a role in some peoples' ability to get rid of the virus without the help of medication. To do this, they assembled information from six different studies that had over many years collected DNA and Hepatitis C infection information from people all over the world. The team then analyzed DNA at the IL28B gene from a total of 1008 patients: 620 persistently infected and 388 who had been infected but no longer carried any virus. DNA analysis revealed that of the 388 patients who no longer carried virus, 264 have the C/C variation.

"This is the strongest clue to date to understanding what would constitute a successful immune response," says Thomas. "We don't yet know the significance of this C variant, but we know we need to do more work to find out what it means and whether it might be helpful to halting the disease."

During the study, an intriguing trend emerged.  For some reason, the C/C variant is not equally spread across populations. 

To investigate further, they analyzed DNA from more than 2300 people worldwide in order to further examine distribution of the C/C variant in different populations. Of the 428 samples from Africa, only 148 carried the C/C genotype. In contrast, of the European samples 520 out of 761 carried the C/C variant. The most striking were the DNA samples from Asia, where 738 of 824 samples carried C/C.

"We wonder if this SNP also explains some of the genetic basis for the population difference of Hepatitis C clearance," says Chloe Thio, M.D., associate professor of medicine. "It's been reported that African-Americans are less likely to clear the disease than Caucasians."

This line of thought will be followed.  The team hopes to find a reason why some populations are more likely to become chornically infected.  "This is an exciting step towards better understanding of what the immune response is against the virus so we can improve our therapies," says Thio

This study was principally funded by the National Institutes of Drug Abuse and the National Cancer Institute of the National Institutes of Health.

Johns Hopkins Center for Viral Hepatitis:
http://www.hopkinsmedicine.org/Medicine/viralhep

The portions of the press release reprinted with permission.