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Gene plays role in early-onset heart disease and diabetes

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Gene plays role in early-onset heart disease and diabetes

When heart disease affects people under age 50, it’s considered “early onset” and experts believe there’s a genetic link. Yale investigators have found that a particular gene is common to families with multiple members who either have early-onset heart disease or who are at risk for it.

By Ziba Kashef

The gene, CELA2A, was discovered at Yale by Arya Mani, M.D., professor of medicine and of genetics, and his colleagues. It produces a protein that regulates other proteins in the pancreas. For this new study, Mani and his co-authors examined individuals in families with early-onset heart disease, and learned that the protein plays a more significant role than previously thought, he said.

The researchers studied 30 cases of families with early-onset heart disease, performing whole genome analyses on close relatives and extended family members. They found a common mutation in the CELA2A gene that blocks its function. They also showed that the gene’s encoded protein circulates outside the pancreas, in the blood, where it affects clotting as well as insulin levels.

In further experiments they demonstrated that in humans the level of this protein rises in parallel with insulin after each meal. Subsequently they showed that insulin levels rose in hypoglycemic mice after the animals were given the CELA2A protein.

These findings show that the gene is a hidden link for diverse risk factors that often occur together in a medical condition known as metabolic syndrome, said the researchers. The clustering of these risk factors — including high blood pressure, high blood sugar, obesity, and abnormal cholesterol — dramatically raises the risk of heart disease and diabetes.

Mani and his colleagues think that many other pancreatic enzymes circulate in the blood and potentially have biological functions. He noted that for decades, scientists studied these circulating enzymes to understand the state of organ damage but never considered them as functional enzymes that could contribute to systemic disease.

With this insight, he said, scientists have a target for new therapies to potentially treat a variety of chronic illnesses, from heart disease and hypertension to insulin resistance, an underlying factor in type 2 diabetes.

source: Yale University

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