Gene mutations that increase the risk of type 2 diabetes also boost the likelihood of heart diseases, according to a study which explains how the two disorders – that are the leading cause of global morbidity and death – are linked. Type 2 diabetes (T2D) has become a global epidemic affecting more than 380 million people worldwide; yet there are knowledge gaps in understanding the etiology of type-2 diabetes. It is also a significant risk factor for coronary heart disease (CHD), but the biological pathways that explain the connection have remained somewhat murky. In an analysis of genetic data, published in the journal Nature Genetics, researchers from University of Pennsylvania in the US, looked into what causes type 2 diabetes. They also clarified how T2D and CHD – the two diseases that are the leading cause of global morbidity and mortality, are linked.
Examining genome sequence information for more than 250,000 people, the researchers first uncovered 16 new diabetes genetic risk factors, and one new CHD genetic risk factor; hence providing novel insights about the mechanisms of the two diseases. They then showed that most of the sites on the genome known to be associated with higher diabetes risk are also associated with higher CHD risk. For eight of these sites, the researchers were able to identify a specific gene variant that influences risk for both diseases. The shared genetic risk factors affect biological pathways including immunity, cell proliferation, and heart development. “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,” said Danish Saleheen, assistant professor at University of Pennsylvania.
“From a drug development perspective, it would make sense to focus on those pathways that are most strongly linked to both diseases,” Saleheen said.
The researchers started by examining sets of genome data on more than 250,000 people, of South Asian, East Asian or European descent. They were able to confirm most of the known diabetes risk sites on the genome – and uncover 16 new ones. The scientists also identified eight specific gene variants that are strongly linked to altered risk for both diseases. Seven of these gene variants, as expected, appeared to increase risk for both diseases. The eighth, a variant of the gene for the cholesterol- transport protein ApoE, is associated with higher diabetes risk but lower CHD risk – a finding that is somewhat puzzling, Saleheen said. However, it is consistent with data from statin trials showing that pharmacologically lowering LDL cholesterol can modestly increase diabetes risk. The researchers also hope to learn more about the biology of the newly discovered dual-risk genes by studying people who have mutations in those genes.