Y-Chromosomes. (©YustynaOlha - stock.adobe.com)
BOSTON — The spontaneous loss of the Y chromosome has been a medical mystery among aging men for quite some time. Now, a new study is linking this condition to an even more concerning problem — death from heart disease. Researchers at Boston Medical Center (BMC) and Boston University (BU) Chobanian & Avedisian School of Medicine have found that men who are losing their Y chromosomes are at a much higher risk of dying from heart disease.
Specifically, the study published in Circulation: Heart Failure explored the risk factors for transthyretin cardiac amyloidosis (ATTR-CA), a common cause of heart disease among older men. Transthyretin amyloidosis occurs when a person’s liver produces faulty transthyretin proteins. Clumps of these abnormal proteins build up in the heart’s main pumping chamber, causing the left ventricle to become stiff and weak.
The analysis uncovered a connection to the spontaneous loss of the Y chromosome (LOY). The more blood cells missing their Y chromosomes, the greater the odds were that a person would die from ATTR-CA.
Study authors note that LOY is one of the most common genetic mutations among men. Over half of the male population who make it to age 90 will lose their Y chromosomes from at least some of their blood cells. Previous studies have also linked the disappearance of the Y chromosome to poorer heart health, but these reports did not examine LOY’s link to ATTR-CA.
“Our study suggests that spontaneous LOY in circulating white blood cells contributes both to the development of ATTR-CA in men and influences the severity of disease,” says Dr. Frederick Ruberg, the Chief of Cardiovascular Medicine at BMC and Professor of Medicine at BU Chobanian & Avedisian School of Medicine, in a media release. “Additionally, our study’s findings indicate that elevated LOY may be an important reason why some patients do not respond to the ATTR-CA therapy that is typically effective.”
Methodology & Results
In total, researchers examined 145 men from the United States and Japan with ATTR-CA and another 91 dealing with heart failure due to an issue other than transthyretin cardiac amyloidosis. Results revealed that men who had lost more than 21% of their Y chromosomes were over two and a half times more likely to die of heart disease than men with intact blood cells.
The Boston team notes that approximately 30% of patients with ATTR-CA do not respond to current treatments. This problem often leads to hospitalization and death from heart failure. Study authors believe their new discovery reveals a key genetic barrier that may be keeping these patients from responding to treatment.
“Our study team represents an international collaboration that sought to explore an association between a common blood disorder and ATTR-CA that has never been previously considered,” Ruberg concludes. “We provide evidence that these two conditions may be related, supporting a new way of understanding how ATTR-CA progresses as well as how to develop new potential targets for treatment.”
