Linkage Analysis Shows Susceptibility to Cold Sores Is Inherited

Six specific genes were pinpointed in that chromosomal region as candidates for making people prone to outbreaks of cold sores (also called "fever blisters”). Cold sores occur when the herpes virus reactivates from its quiescent state within the nerve, infecting the lip, nose, or face.

Herpes simplex virus type 1 (HSV-1) is responsible for the vast majority of cold sores, the most common recurring viral infection in humans, as well as herpes keratits, an eye infection that can lead to corneal scarring and blindness. The majority of the U.S. population is infected with HSV-1, although millions of people manifest no symptoms. Nonetheless, at least 40% of the population will experience at least one cold sore at some point during their lives.

To search for cold sore susceptibility genes, University of Utah (Salt Lake City, UT, USA) investigators used linkage analysis, which traces genetic markers in families to identify regions on chromosomes that harbor disease genes. When genetic mutations are passed from parent to offspring, genetic markers near the disease gene are passed along as well. By identifying markers shared among family members, scientists can locate regions of chromosomes where genes responsible for disease may lie. The study was the first whole-genome study of HSV to use linkage analysis.

Four hundred and twenty-one people from 39 large Utah families were studied. The families are part of a genomic study called the Utah Genetic Reference Project. Participants were grouped according to how often they experienced cold sore outbreaks: frequently affected--at least two or more outbreaks of HSV-1 annually; mildly affected--two or less outbreaks annually; unaffected--HSV-1 infected but had never experienced an outbreak; and unknown or HSV uninfected--not categorized.

The uncategorized and mildly affected groups were excluded from the study. When all the genetics data were collected, a mathematical analysis determined the odds of a link between cold sores and the long arm of chromosome 21 to be at least 1,000-to-1. The probable genetic link is not the only component believed to trigger reactivation of HSV and cold sores. Environmental factors, such as fever, wind, and sunburn, as well as viral factors, such as strain and burden of latent infection, also influence the frequency of HSV outbreaks. Discovery of the probable link could lead to the development of new drugs that reduce the frequency of herpes outbreaks.

The study was reported in the February 1, 2008, issue of The Journal of Infectious Diseases and is available online.


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