University of Utah researchers have used linkage analysis to show a likely genetic susceptibility to cold sore outbreaks. And they think they've narrowed the search for the genes responsible to six likely candidates in the area of chromosome 21.
The findings will be released Friday in The Journal of Infectious Diseases and the researchers hope it will ultimately lead to medications to treat outbreaks and reduce their frequency, said Dr. John D. Kriesel, the study's corresponding author and research associate professor in the U. medical school's Division of Infectious Diseases.
Maurine R. Hobbs, Ph.D., research assistant professor in the Division of Endocrinology and Metabolism, is the study's first author.
Cold sores, the most common recurring viral infection in people, are caused by type 1 of the herpes simplex virus (HSV-1). Once an outbreak subsides, the virus stays "quiescent" within the nerve until it reactivates. It's believed at least 40 percent of Americans will have at least one cold sore at some point. The virus also causes herpes keratitis, an eye infection that can damage the cornea and even cause blindness. HSV-2, the second kind of herpes simplex virus, is the primary cause of genital herpes.
Using families within the Genetic Reference Project as subjects, researchers analyzed blood of more than 400 people in 39 big Utah families to determine who had the HSV-1 virus. Then they asked them questions about their experience with cold sores, said Kriesel. They subdivided those with the infection into three groups based on frequency of cold sore outbreaks, then studied those at the extremes of the spectrum, who had either never experienced a cold sore or who had them at least twice a year.
Linkage analysis uses genetic markers in families to find regions on chromosomes that have disease genes. The markers are passed from parent to child along with the genetic mutation. So if they find markers shared by family members, the researchers can zero in on regions of chromosomes where the genes may lie. It's the first whole-genome study of HSV to use that analysis.
The program said the odds are 1,000-to-1 that the area around chromosome 21 is involved in cold sore outbreaks.
They also wanted to determine the degree to which outbreaks are heritable, Kriesel said. Huntington's disease is entirely genetic, although it's not always passed on. Alcoholism and schizophrenia are both believed to be 20 to 40 percent heritable.
The researchers found that cold sore outbreaks are about 20 percent heritable. "That's very significant, but it means about 80 percent of the disease is due to other stuff. Do you ski without sunscreen on your lips? Are you prone to febrile illnesses? What strain of virus did you get?" Kriesel said.
They believe, he said, that the individual's own factors, the infection's viral load and similar factors and the environment all play a role in expression of the disease.
"We think that for people who get frequent reactivations, it's likely there are more than one susceptibility gene," Kriesel said.
They plan to do genotypings within the candidate genes to see what else they can learn about cold sores and genetics. Three of the six genes, in particular, look promising.
Co-authors, besides Hobbs and Kriesel, are Mark F. Leppert, Ph.D., distinguished professor and co-chairman of the Department of Human Genetics; Brandt B. Jones (B.S., senior research scientist), Division of Infectious Diseases; and Brith E.M. Otterud (B.S., computer professional), Department of Human Genetics.
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