Cold Sores Likely Caused by One of Six Genes

Cold sores are the most common recurrent viral infection that people get-and University of Utah medical researchers say there's a good chance that a predisposition to them is inherited through one of six genes.

Researchers from the U of U School of Medicine and Eccles Institute of Human Genetics have traced susceptibility to cold sores, also known as fever blisters, to a region of six genes on human chromosome 21. Herpes simplex virus 1 (HSV-1) causes the sores, but while most people are infected with this virus, only some get frequent cold sores.

A mathematical analysis computed the odds of linkage from one of the six genes to cold sores at 2,500:1-strong enough to indicate a correlation, said John D. Kriesel, M.D., assistant research professor of internal medicine.

The six candidate genes had not previously been linked to cold sores. More research needs to be done to determine which of the six candidates actually causes frequent cold sores.

"There is very likely a human susceptibility gene for herpes simplex virus recurrences," said Kriesel, who presented the findings Sunday at the Infectious Disease Society of America's annual meeting in Chicago.

That gene may be passed down in families, and could be dominant or recessive.

Along with Kriesel, the U of U researchers include Mark F. Leppert, Ph.D., professor and co-chair of the Department of Human Genetics; Spotswood L. Spruance, M.D., professor of internal medicine; Andreas Peiffer, Ph.D., research assistant professor of pediatrics; Brith Otterud, computer specialist; and Brandt Jones, senior lab specialist.

Besides being a first-rate annoyance for those who get them, cold sores also can lead to more serious diseases-ocular herpes, which sometimes causes blindness, and genital herpes.

With that in mind, the U researchers started looking for a genetic link to cold sores in 1998. They began their search by combing through a database of 45 multigenerational families-350 people-in the Utah Genetic Reference Project (UGRP). UGRP was assembled under the direction of Leppert to create genetic marker maps of human chromosomes for a database to study diseases.

The U researchers eventually narrowed the database to 87 people in nine families who already have HSV-1 infection. The 87 were divided into two groups: those who don't get cold sores, and those who get two or more a year. The two groups were compared in a computer analysis that assumed dominant and recessive modes of inheritance and linked genetic markers with the common traits of cold sores. The computer analysis concluded that a region on human chromosome 21, including six candidate genes, is likely linked to cold sores, according to Kriesel.

While the researchers are confident one of the genes is linked to cold sores, they don't say the study is definitive. They've applied to the National Institutes of Health for a grant to expand the research to include more families and identify a specific gene.

One of the next issues to examine, according to Kriesel, is whether the region where the six genes reside varies between people with and without ocular and genital herpes.

Ultimately, if the researchers identify a specific gene that leads to cold sores, they may be able to find a way to prevent them.

"The next step is to counteract that gene," Kriesel said.