Small Changes, Big Heart Problems

Heart disease in patients with type 2 diabetes associated with small genetic variants

(RxWiki News) Heart disease is a common complication of type 2 diabetes. Yet it is still not clear how diabetes boosts the risk of heart disease. Part of the answer may lie in our genes.

Researchers have discovered a genetic change that is associated with heart disease in patients with type 2 diabetes. It is not likely that this small gene variant is the cause of heart disease, but it could point to a gene that may serve as a future target for treating heart disease.

"A small genetic change is a sign of heart disease in diabetes patients."

Sharon Cresci, M.D., of Washington University in St. Louis and first author of the study, and colleagues identified a change in a person's DNA located in a gene called TLL1. This gene is involved in inflammation and the hardening of blood vessels.

According to Richard G. Bach, M.D., also from Washington University and one of the study's authors, there is a knowledge gap in the understanding of diabetes and how it leads to heart disease and poorer results for diabetes patients. Any additional information about what is causing this could help patients in the future, he adds.

Researchers investigating diabetes and heart disease have not been looking at TLL1 and related genes, says Dr. Cresci. By looking at this genes, Dr. Cresci and colleagues found a variant in one or two letters of a person's DNA sequence (DNA has a four-letter "alphabet" consisting of A,C,G, and T).

'TT' is the most common sequence in this part of the TLL1 gene. Patients who had 'CT' in that part of the sequence had 22 percent more coronary lesions (damage to blood vessels) that blocked blood supply to the heart, compared to those with the normal 'TT' sequence. Patients with 'CC' in the sequence had it even worse: 37 percent more lesions than those with 'TT'.

Each of these two-letter variants also changes the amount of lesions on the average patient in the study, which was a 63-year-old white male with a BMI of 30.

On average, a patient with the 'TT' sequence would have 4.43 lesions. However, the average patient with a 'CT' sequence would have 5.02 lesions. The number of lesions increases all the way to 5.46 if that patient has the 'CC' sequence.

Dr. Cresci notes that the differences in the number of lesions may be small. But these changes are determined by just one small variant, she explains. For being just one variant, it has a particularly strong connection to the severity of heart disease.

“In an ideal situation," says Dr. Cresci, "you would select drug treatment based on the individual’s DNA sequence. Maybe the people with the TT genotype would get one medication, but the ones with CC would get different therapeutics. Obviously, we’re a long way from that, but that’s where we would like to be. And that is where work like this is going.”

All the participants in the study were part of a clinical trial called Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D). They all had type 2 diabetes and heart disease. However, their arteries had not become so blocked that they needed surgery right away. A group of the patients had their DNA sequenced for the genetic part of the study.

The results of this study are published in Circulation

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Review Date: 
September 29, 2011