Researchers find genetic mutation in peripheral artery disease

Researchers have shed light on how peripheral artery disease or PAD develops and progresses in humans, by finding a genetic mutation in the disease.

Washington, Feb 24 : Researchers have shed light on how peripheral artery disease or PAD develops and progresses in humans, by finding a genetic mutation in the disease.

Peripheral arterial disease occurs when major arteries in the legs become clogged with plaque, a fatty build-up that's similar to the deposits in coronary arteries that can lead to a heart attack.

Its symptoms range from leg pain brought on by walking that goes away with rest to a more serious form, marked by continuous pain and sores and ulcers on the legs that often lead to amputation.

The mice based study, led by Dr. Brian Annex, professor of medicine and director of vascular medicine at Duke, is likely to give a new insight into how PAD develops and progresses in humans. nnex said that the study stemmed directly from his clinical experience.

"Over and over, I'd see two patients show up at the same time. They would be the same sex, same age, have identical risk factors and have similar blockages in their arteries. One of them would experience very slow progression of the disease, while the other would face limb loss or death within six months. I just knew there just had to be a genetic basis for it," Annex said.

Annex added that the mild form of the disease rarely progresses into the more severe form.

"In reality, we may be looking at two types of diseases, although we've always thought of PAD as one," he said.

In the study, the research team had two strains of mice with surgically induced blocked blood flow that mimicked human response to PAD. One strain recovered well, showing restored blood flow and little tissue death; the other had greater tissue loss and poor recovery of normal blood flow.

In collaboration with Dr. Douglas Marchuk, a professor of molecular genetics and microbiology at Duke, researchers crossbred the two strains and eventually isolated a mouse that enabled them to identify a relatively small region on chromosome 7 that appears to protect the mice from the consequences of the surgically-induced, PAD-like injury.

"Essentially, we now have a field of about 20 genes that we think may be involved in shaping the way peripheral artery disease develops," said Annex.

"At this point, we are not certain which ones are playing an active role, however. Still, we feel strongly that our discovery opens a new wave of investigation that may one day yield novel prevention strategies or treatments," he added.

The study is published in the journal Circulation.

ANI