Genetic mutation made humans susceptible to heart attacks – study

This article was taken from: https://www.theguardian.com/society/2019/jul/22/genetic-mutation-made-humans-susceptible-to-heart-attacks-study

By Anna Ploszajski

Gene that helped prevent clogged arteries was lost 2 to 3 million years ago

The loss of a single gene 2 to 3 million years ago in our ancestry may help explain why humans are the only animals in which heart attacks are common.

Atherosclerosis – the clogging of arteries with fatty deposits – can lead to cardiovascular disease (CVD) events like heart attacks and strokes, which cause about a third of all deaths worldwide.

An inactive lifestyle, age, diabetes, obesity, smoking, and eating red meat can all contribute to an increased risk, but about 15% of first-time CVD events occur in people who do not have any of these risk factors.

However, heart attacks are very rare in some of our closest genetic relatives, like chimpanzees – even those with high cholesterol and a sedentary lifestyle.

“That’s always been a puzzle,” said Prof Ajit Varki at the University of California San Diego School of Medicine, who has led new research into the genetic mechanism. “What’s unusual about humans?”

Two to 3 million years ago, our ancestors acquired a genetic mutation that inactivated a gene called CMAH, making us deficient in molecules called sialic acids. In the study, published in PNAS, researchers genetically modified mice to be more like humans in their deficiency of a sialic acid sugar molecule called Neu5Gc. They found the atherosclerosis in these mice was nearly twice as severe as that in unmodified mice.

The study also looked specifically at the effect of eating red meat. When humans eat animal flesh which contains Neu5Gc molecules, “it’s like a Trojan horse”, said Varki. “It sneaks in and causes an inflammatory immune response.”

To mimic this effect, the researchers fed the genetically modified mice a high-fat diet which was rich in Neu5Gc. These mice suffered an increase in atherosclerosis 2.4 times that of unmodified mice fed the same diet.

“This is interesting, possibly groundbreaking work, particularly their evolutionary approach and the link to metabolism,” said Dorian Haskard, professor of cardiovascular medicine and rheumatology at Imperial College London, who was not involved in the study.

But he warned against extrapolating the mouse study to humans. “The changes seen in a mouse may be very different from those in a human,” he said. “In a mouse study, the disease is greatly accelerated, so there needs to be much more work done on the association with humans.”

Prof Metin Avkiran, associate medical director at the British Heart Foundation, said: “Learning from naturally occurring genetic variations between humans is already improving our understanding of the atherosclerotic disease process and powering the development of new treatments. A better understanding of inter-species differences through research such as this also has the potential to lead to similar advances.”

Although atherosclerosis can have devastating effects on the body, the inactivation of the CMAH gene itself is not all bad. “This is a permanent mutation in humans – we can’t reverse it,” said Varki. “Actually, we don’t want to reverse it because it has many other effects. For example, it helps to explain why humans are very good at running long distances.”

Varki said he now hoped to develop “an antidote to red meat to allow people to consume a moderate amount, which would give them the nutritious benefits, but without the negatives”.