Genes Link Type 2 Diabetes, Coronary Heart Disease

The genomes associated with a higher risk of CHD are also associated with higher T2D risk, revealing the possibility of a treatment for both.

Type 2 diabetes (T2D) and coronary heart disease (CHD), the leading causes of illness and death worldwide, are linked by genes, a new study has found.

Researchers have already documented that T2D is a significant risk factor for CHD, with diabetes patients facing twice the risk of developing the heart ailment. However, the biological pathways that explain the connection have remained unclear.

Now, a team at the University of Pennsylvania’s Perelman School of Medicine has discovered that locations on the genome associated with higher diabetes risk are also associated with higher risk for CHD.

That finding could pave the way for new medications to treat both diseases, according to study co-senior author Danish Saleheen (pictured), MBBS, PhD, and an assistant professor of biostatistics and epidemiology at Penn.

“Careful evaluation of the pathways or biological processes where T2D, CHD, and related traits overlap could help to highlight new avenues for therapeutic targeting,’’ the researchers said. The team began its investigation by examining genetic data on more than 250,000 people of Asian and European descent.

“We knew that there would be a set of genetic pathways that would connect T2D with CHD; however, it would take us thousands of participants to identify those pathways,” Saleheen told MD Magazine. “Hence we undertook a study that involved at least 250,000 participants for each outcome.”

The researchers discovered 16 new genomic regions that cause T2D and one that causes CHD, according to Saleheen. “Additionally, we identified at least seven risk variants associated with T2D that also increase the risk of CHD,” he added.

The team also found 79 high probability regions in the genome that are enriched for associations for both T2D and CHD. Many of these areas are targets of existing drugs, including adipocyte fatty acid binding protein and icosapent ethyl, Saleheen said.

The genetic link between diabetes and heart disease appears to work in 1 direction, the researchers reported. For example, risk genetic variants for T2D are much more likely to be associated with higher CHD risk than the reverse.

Diabetes-linked gene variants also tend to differ in their apparent effects on CHD risk, depending on their mechanisms. Variants that increase the chance of obesity or high blood pressure seem to boost CHD risk more strongly than variants that alter insulin or glucose levels, the study found.

Saleheen cautioned that there could be some pathways where using drugs to treat 1 disease could raise the risk of the other.

“It is important that the both the existing and new drugs for T2D or CHD have either neutral or beneficial effects on the other outcome,” he said. “We would certainly like to stay away from the drugs that confer protection from one disease but increase the risk of the other.”

For example, cholesterol lowering statins prevent the risk of CHD but raise the risk of T2D, Saleheen noted.

The team will continue to study biomarkers, cell and animal models and “human knockouts,” or individuals who are deficient of genetic products, to investigate the newly found genomic regions in greater depth, according to Saleheen. He added that such research is important.

“Diabetes is going to affect half a billion people globally by the next two decades,” Saleheen said. “Coronary heart disease (CHD) is the leading cause of death globally.”

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