A research team led by doctors from the Viral Hepatitis Group of Hopkins Hospital's Division of Infectious Diseases has discovered that a genetic difference in a single nucleotide may be the reason some people spontaneously recover from hepatitis C.
The researchers analyzed genetic data collected during six previous studies of hepatitis C patients and found that those who had two cytosine nucleotides were three times more likely to recover without treatment than those with cytosine-thymine nucleotides or two thymines.
Their findings might also explain why different ethnic groups have different rates of spontaneously clearing the disease.
Hepatitis C is caused by the blood-borne hepatitis C virus. Most infected people initially show few, if any, symptoms, and are unaware that they are infected until the disease becomes a chronic infection. Chronic hepatitis C in the most serious cases leads to liver failure, cirrhosis or cancer. There is no vaccine, but about 30 percent of patients spontaneously clear the virus, recovering completely with no treatment.
The single nucleotide polymorphism - that is, a genetic variation consisting of a single nucleotide difference between two homologous chromosomes, one from each parent - is found about three kilobases upstream of a gene that codes for a member of the interferon group of proteins. Interferons are produced by our immune cells in response to viral infection. They help activate other members of the immune system which attack the virus or prevent its spread.
Some people's DNA happens to contain two cytosine nucleotides (C/C), with one in each chromosome at the same spot of the pair, while others contain a cytosine and thymine (C/T) or two thymines (T/T). This suggests that the protection by this allele is a recessive trait.
Although the SNP site is not actually located within the interferon gene, it is believed to affect the immune response to hepatitis C infection. A previous study conducted at Duke University showed that people with the C/C genotype, or cytosine nucleotides at both sites, responded much better to drug treatments for hepatitis C than those without it. This study sought to examine how that genotype affected hepatitis C patients in nature.
"We are trying to determine better ways to treat and prevent hepatitis C infection," David Thomas, who led the study along with Chloe Thio, said. "We would like to understand why this genetic difference was detected. It might point the way to new treatments, better ways to select patients for treatment and may be even ways to prevent hepatitis C."
The research team found that about 53% of patients with the C/C spontaneously cleared hepatitis C. This figure is significantly higher than the 30% of the general population expected to clear the disease. In fact, 28% of patients with the C/T or T/T genotype recovered without treatment-close to the expected percentage. Of the total 388 patients who cleared the virus, 264 had the C/C variation. The study calculated that people with the C allele were three times more likely to clear the infection.
The study also found significant differences between the frequency by which the C allele was found in different ethnic groups, which might help explain the different rates of spontaneously clearing hepatitis C in those groups.
Although the general patterns remained the same, the C allele is found much more frequently in people of European ancestry than in people of African ancestry. These findings are consistent with the rates of hepatitis C clearance in both groups; 36.4% of infections clear spontaneously in patients with non-African ancestry, compared to 9.3% in patients with African ancestry.
"We think this finding might explain why African-Americans tend to get chronic infection more than Caucasians," Thomas said.?"We are doing another study to figure that out."
Worldwide, the C allele is almost prevalent in east Asia, intermediate in Europe, and in the minority in Africa. Although scientists have yet to understand exactly how this allele protects us, their findings have opened up the possibility for different treatments and even vaccines for hepatitis C based on genetic information.
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