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Genomic Signatures of CVD in Twins Discordant for Smoking

Institution: University of California, San Diego
Investigator(s): Brinda Rana, PhD
Award Cycle: 2014 (Cycle 23) Grant #: 23RT-0015 Award: $445,311
Subject Area: Early Diagnosis/Pathogenesis
Award Type: Research Project Awards

Initial Award Abstract

Cigarette smoking is an established independent risk factor for the development and progression of cardiovascular disease (CVD). Recent studies have shown that cigarette smoking and tobacco exposure can alter the structure of our genetic material, in particular, our telomeres. Telomere are segments of our DNA molecule which protect our genetic material from deterioration. Telomeres shorten with age and also with environmental trauma. Thus, telomere length can be reflective of our cells' "molecular age". Smoking has been shown to accelerate telomere shortening. Smoking has also been shown to alter DNA methylation patterns. DNA methylation controls which genes are "expressed" or functioning in our cells and tissues.

Both shortened telomere length and altered DNA methylation patterns have been associated with CVD. It is the goal of our study to identify patterns of changes in telomere length and DNA methylation that are associated with smoking-induced CVD. We will use a population of twin brothers in which one brother is a smoker and the other is a non-smoker. Twin are a powerful tool for such studies because the non-smoking twin provides the ideal approximation for the traits that his smoking twin would display if he did not smoke. Differences between the twin brothers are then most likely due to smoking rather than inherited differences.

Our study can provide novel information of physiological pathways that are changed by cigarette smoking and may lead to CVD. Understanding these pathways can be useful in developing tests that the physician can use for the early prediction of tobacco-related CVD. Although the best strategy for preventing tobacco-related CVD is to reduce smoking, our study provides an alternative approach to developing preventive measures for tobacco-related CVD risk when tobacco exposure cannot be avoided.