A new grant to San Antonio's Southwest Foundation for Biomedical Research (SFBR) will allow scientists to look for genetic factors that increase our susceptibility to some of this countrys most common chronic infections, and ultimately, how that susceptibility might be linked to our risk for cardiovascular disease.
Dr. Harald Göring, principal investigator of the new $1.9 million grant from the National Heart, Lung and Blood Institute, titled Genetics of Infection and its Relation to CVD Risk, says there has not been extensive research on the role infections play in the risk for cardiovascular disease. However, a number of epidemiological studies have shown a higher-than-average prevalence of infections among people who have suffered heart attacks, strokes, and a variety of other ailments.
He says a leading hypothesis explaining this correlation is that chronic infections lead to a chronic state of inflammation, as the immune system works continuously to fight off the infection. In recent years, it has become apparent that inflammation is a central feature of some chronic diseases of old age, and its particularly well-established as a risk factor for atherosclerosis and cardiovascular disease, Göring said.
So the obvious question becomes, What gives rise to inflammation? he continued. Inflammation typically has some underlying cause, something that leads the immune system to respond to something. Its not unreasonable to think that a chronic infection with some type of virus or bacterium even if that infection is not causing acute symptoms would keep the immune system continually at work and lead to some overall systemic inflammation, as well as inflammation at a specific site [in the body] where the pathogen might be hiding.
Therefore, he says, if we could find better ways to control infections, we might in the process reduce risk for cardiovascular disease and other conditions affected by inflammation.
To study this whole issue, Göring is collaborating with Drs. Charles Leach and Ellen Kraig at the University of Texas Health Science Center at San Antonio in a close look at participants from three major San Antonio studies: the San Antonio Family Heart Study, the San Antonio Family Diabetes/Gallbladder Study, and the Veterans Affairs Genetic Epidemiology Study. All three studies involve large, multi-generational family groups from the San Antonio area; all are focused on the genetics of metabolic diseases, where inflammation plays a major role; all involve Mexican Americans, so participants are from the same ethnic background; and all have genetic samples and various health measures readily available for examination in this new study. Using data from 2,500 participants of these three studies, Görings first goal is to determine how many of these individuals test antibody-positive for current or previous infection with one or more of seven selected pathogens, and then to search for genes that influence their susceptibility to infection with these pathogens.
For this study, we specifically selected seven infectious agents that have shown some correlation with cardiovascular disease, that are capable of eliciting chronic infections, that are transmitted through the respiratory tract, and that are so common in the environment that we can presume just about everyone has been exposed to them multiple times, said Göring.
These pathogens include Chlamydia pneumonia, a common cause of pneumonia; Helicobacter pylori, a major cause of ulcers; Porphyromonas gingivalis, commonly associated with gum disease; hepatitis A virus, most commonly spread among school-age children and young adults; herpes simplex virus 1, the cause of cold sores; Cytomegalovirus, or human herpesvirus 5, which particularly affects the salivary glands; and human herpesvirus 8, which induces Kaposi sarcoma in persons with immunodeficiency.
What we want to know is, since these pathogens are so common and so easily spread, how have some people managed to avoid infection? asked Göring. Everyone has been exposed to them, but some people dont have antibodies for them in their bloodstream, indicating that theyve never been infected with these pathogens and mounted an immune response. So they may have some innate resistance to infection, some other way of preventing infection in the first place. That could be due to a difference in their genetic makeup.
In a pilot study with 600 individuals from the San Antonio Family Heart Study, Göring has already shown evidence that there are genetic variants on chromosome 21 that influence susceptibility to Chlamydia pneumonia. Now he wants to look for genetic influences on susceptibility to all seven pathogens in a larger study population.
In addition, he plans to examine the study population to see if there is a correlation between infection with these pathogens and markers for inflammation, such as high levels of C-reactive protein. That could help validate the hypothesized link between infection and cardiovascular disease, and it could allow Göring to search for genes that influence both.
He believes the study could have multiple payoffs for human health. The more we know about the relationship of infection and inflammation, the more likely people are to try to decrease infection levels, he said. And certainly, its feasible to treat many bacterial infections with antibiotics. But if we can find genetic factors that influence susceptibility to infections, it might also provide new ideas for how to design effective vaccines.
Besides that, There are so many things that we still dont know about our immune system and how it works, he said. Potentially, the identification of genetic factors involved in fighting infections might tell us something new about the function of the immune system and give us new ideas for fighting disease.