Researchers from Boston Medical Center (BMC) and Boston University (BU) Chobanian & Avedisian School of Medicine, in collaboration with an international team of scientists, shared the results of a new study published in the Journal of the American Heart Association. Circulation: Heart failure A research team studying transthyretin cardiac amyloidosis (ATTR-CA), a common cause of heart disease in older men. The study examines the relationship between spontaneous loss of Y chromosome (LOY) (a condition in which the Y chromosome is spontaneously lost from blood cells) in older men and ATTR-CA, a progressive disease that can cause heart failure and death. The team found that men with a higher percentage of blood cells lacking the Y chromosome were more likely to die from ATTR-CA, which could help inform future treatment of ATTR-CA patients. The research team includes researchers from Columbia University, University of Virginia, and Osaka Metropolitan Hospital in Japan.
LOY is the most common acquired genetic mutation in men, with more than half of men in their early 90s losing the Y chromosome in some of their blood cells, according to the National Cancer Institute. Large population studies have reported that LOY is associated with survival from heart failure, but it has never been investigated in relation to ATTR-CA. This study suggests that men with ATTR-CA who have LOY in 21.6% or more of their blood cells are 2.6 times more likely to not survive this type of heart disease.
“Our study suggests that naturally occurring LOY in circulating white blood cells contributes to the development of ATTR-CA in men and also influences disease severity,” said Frederick L. Luberg, MD, chair of the Department of Cardiovascular Medicine at BMC and professor at the Boston University Chobanian-Avedisian School of Medicine, and lead investigator on the study. “Furthermore, our findings suggest that elevated LOY may be an important reason why some patients fail to respond to normally effective ATTR-CA therapies.”
Although current treatments for ATTR-CA are effective for many patients, approximately 30% of patients do not respond to treatment, leading to hospitalization or death. The results of this study support that elevated LOY is a potential barrier to treatment response. In the future, these results may help clinicians design treatment courses for patients with ATTR-CA and high levels of LOY and select those with the hope of more favorable health outcomes. Furthermore, these results may lead to the development of new treatments for patients with cardiac disease, including ATTR-CA.
“Our research team represents an international collaboration seeking to explore the association of ATTR-CA with common blood disorders that have not been considered before,” Luberg says. “We provide evidence that these two diseases may be related, supporting a new way of understanding the progression of ATTR-CA and developing new potential targets for treatment.”
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Journal References:
Teru, MC, etc (2024). Mosaic deletions of the Y chromosome are common in patients with wild-type transthyretin cardiac amyloidosis and are associated with increased mortality. Circulation. Heart failuredoi.org/10.1161/circheartfailure.124.011681.