Dependence of Longevity and Health on TRB3 Genotype

Anthony J. Muslin, M.D.

Project Overview:
The prevalence of adult-onset sugar diabetes is increasing in the United States. Diabetes is associated with the development of a serious disease of the blood vessels, atherosclerosis that causes heart attacks and strokes. In adult-onset diabetes, insulin does not work properly, and muscle and fat do not take up sugar from the blood stream. A newly identified protein, called TRB3 (“trib three”) was found to inhibit the action of insulin, and this new protein may play a role in the development of diabetes and disease of the blood vessels. Chromosomal DNA contains genes that encode proteins that are made inside of cells. The gene that codes for the TRB3 protein is changed in about 15% of people, and that change is called a single nucleotide polymorphism (SNP, “snip”). The SNP in the TRB3 gene causes the TRB3 protein to be more effective at blocking insulin action. Therefore, people with the TRB3 SNP are predicted to be more likely to develop diabetes and more likely to get atherosclerotic disease of blood vessels. In this project, we will look for the TRB3 SNP in patients that are admitted to the hospital with heart attacks. We will obtain blood from these patients, and analyze DNA in blood samples for the presence of the TRB3 SNP. We will compare the DNA results with the results of the physical examination of the patients, their hospital course, and with other blood tests, such as cholesterol and blood sugar tests. We will try to determine whether the TRB3 SNP is associated with an increased incidence of high cholesterol and a worse prognosis after heart attack. In this way, we will be able to identify people that are at higher risk for these diseases, and enable effected individuals to be treated more aggressively with drugs that lower cholesterol or that lower blood sugar at an earlier point in their life to prevent the development of serious complications.