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GEN News Highlights : Sep 17, 2009

Researchers Pinpoint Genetic Alteration That Is Strongly Associated with the Ability to Get Rid of HCV

The variant is unequally distributed among European, African, and Asian populations, according to Nature paper.

A group of researchers have found that the C/C variant near the IL28B gene is associated with some people’s ability to get rid of HCV. They also report that the variant seems to appear more among European people than Africans and the most among Asian populations.

The results appear in this week's advanced online publication of Nature. The paper is titled “Genetic variation in IL28B and spontaneous clearance of hepatitis C virus.”

A previous study led by David Goldstein at Duke University found a variation in a SNP near the IL28B gene. While poorly understood, it is thought to help the immune response to HCV infection. People infected with hepatitis C, who carried the C/C variant SNP near their IL28B gene, were found more likely to respond to hepatitis C treatment to get rid of the virus.

Thus a Johns Hopkins and NIH-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. They assembled information from six studies that had collected DNA and hepatitis C infection information from people all over the world over many years. The group then analyzed DNA at the IL28B gene from a total of 1,008 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 the virus, 264 had the C/C variation. “This is the strongest clue to date to understanding what would constitute a successful immune response,” says David Thomas, M.D., professor of medicine and director of infectious diseases at Johns Hopkins. “We don't yet know the significance of this C/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.”

In addition to confirming that the C/C variant correlates with the ability to get rid of the virus once infected, the researchers also noticed an intriguing trend: The C/C variant does not appear equally in all populations.

To investigate further, they analyzed DNA from more than 2,300 people worldwide. Of the 428 samples from Africa, only 148 carried the C/C genotype, or about 34.58%. In contrast, 68.33% of European samples, or 520 out of 761, carried the C/C variant. The most striking were the DNA samples from Asia, where 89.56% of the samples, or 738 out of 824, 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.”