The link between type 2 diabetes and coronary heart disease (CHD) is becoming clearer.
Researchers from the Perelman School of Medicine at the University of Pennsylvania have identified 16 new diabetes genetic risk factors and one new heart disease risk factor after examining the genome sequence information for more than 250,000 people of South Asian, East Asian or European descent.
The research team provided new insights about the mechanisms of the two diseases and showed that most of the sites on the genome associated with higher diabetes risk are also associated with a higher CHD risk.
“Identifying these gene variants linked to both type 2 diabetes and CHD risk in principle opens up opportunities to lower the risk of both outcomes with a single drug,” study co-senior author Danish Saleheen, Ph.D., an assistant professor of Biostatistics and Epidemiology, said in a statement. “From a drug development perspective, it would make sense to focus on those pathways that are most strongly linked to both diseases.”
Half of the identified sites had a link to a specific gene variant that influences risk for both diseases and the shared genetic risk factors affect biological pathways, including immunity, cell proliferation and heart development.
Of the eight specific gene variants strongly linked to altered risk for both diseases, seven appeared to increase risk for both diseases. The eighth—a variant of the gene for the cholesterol-transport protein ApoE—was associated with a higher diabetes risk but a lower CHD risk.
They also discovered that the risk genes for type 2 diabetes are much more likely to be associated with higher CHD risk as opposed to the opposite.
“Using evidence from human genetics, it should be possible to design drugs for type-2 diabetes that have either beneficial or neutral effects on CHD risk,” Saleheen said. “However it is important to identify and further de-prioritize pathways that decrease the risk of type-2 diabetes but increase the risk of CHD.”
The researchers also discovered that the genomic regions implicated as dual diabetes-CHD risk locations that encompass targets of some existing drugs and diabetes-linked gene variants, tend to differ in their apparent effects on CHD risk, depending on their mechanisms.
Type 2 diabetes impacts more than 380 million people globally.
“I’m hopeful that with the advanced genomic engineering techniques now available, we’ll be able to quickly convert our human genetics observations into concrete details regarding the molecular mechanisms involved in both heart disease and diabetes,” co-senior author Benjamin Voight, Ph.D., an associate professor of Genetics, said in a statement.