UTHCT researcher receives $1.25 million NIH grant to expand his study of genetic mutations linked to susceptibility to TB

Monday, September 25, 2006

Pedro Flores-Villanueva, MD, associate professor of immunology at The University of Texas Health Science Center at Tyler, recently received a five-year, $1.25 million grant from the National Institutes of Health to fund further research into how small genetic mutations increase a person’s odds of developing active tuberculosis.

“We are focusing on the genetic factors that control the variability of the immune response, factors that may increase the chance of someone developing tuberculosis after being infected with the bacterium that causes TB,” Dr. Flores-Villanueva said. Results of his previous research published in December 2005 indicate that many adults who develop TB carry a mutation in a specific gene.

“This new study will help us test a second gene that probably interacts with the first gene to make people susceptible to tuberculosis. It’s an expansion of our initial research, to confirm our findings and to search for other genes that interact with this one,” Dr. Flores-Villanueva said. Genetic samples will be taken from 5,000 people with TB – 2,500 Mexicans and 2,500 Peruvians – and analyzed to see how many of these individuals have this second gene, he said.

“Our hypothesis is that several genes interact with each other – together with environmental factors such as nutrition and lifestyle – to increase the chances of developing the disease,” Dr. Flores-Villanueva said.

Genes create proteins, which are crucial to pathways, or operations, inside the cell, Dr. Flores-Villanueva said. Once you identify what pathways are affected by changes in these proteins, you can develop new therapies to protect vulnerable individuals from developing tuberculosis.

Worldwide, it is estimated that almost one billion people will become newly infected with TB, more than 150 million will become sick, and 36 million will die between now and 2020, unless the spread of TB is better controlled. Each year there are more than 8.8 million cases and close to two million deaths attributed to tuberculosis; 100,000 of those deaths occur among children.

Tuberculosis is a chronic bacterial infection that usually targets the lungs, though other organs sometimes are involved. Most people infected with TB do not have symptoms of the disease; they have a latent tuberculosis infection. Tuberculosis symptoms include a low-grade fever, night sweats, fatigue, weight loss, and a persistent cough.

Although TB is not easily spread from person to person, once the disease becomes active it can spread to other people. The person with TB coughs or sneezes and the airborne TB bacteria are inhaled by another person who then may develop tuberculosis. You must be in close contact with someone with active TB to contract the disease.

Ninety percent of those infected with tuberculosis will not develop disease, Dr. Flores-Villanueva said. However, 10 percent will develop active TB, and half of those will contract the disease in the first year after their exposure. The rest will develop TB sometime in their lifetime.

Individuals with HIV/AIDS, other pulmonary diseases besides TB, and those taking drugs to suppress their immune system will not be included in the study, Dr. Flores-Villanueva said. In addition, researchers will control for malnourishment and other environmental factors that might make people more susceptible to TB infection.

Also participating in the research are Dr. Julio Granados in Mexico and Dr. Juan Carlos Gomez in Peru. Dr. Flores-Villanueva is the primary investigator of the NIH grant. His UTHSCT research team consists of Jorge Ruiz Morales, MD, Ph.D., and Malathesha Ganachari, Ph.D.

NOTICE: Protected health information is subject to electronic disclosure.