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Researchers Find Gene Variant Linked To Aortic Valve Disease

NIH-funded consortium finds connection between lipoprotein(a) and valve calcification  

A newly identified genetic variant doubles the risk of calcium buildup in the heart’s . Calcium buildup is the most common cause of , a narrowing of the that can lead to heart failure, stroke, and sudden cardiac death.  

An international genomics team called CHARGE ( in Genomic Epidemiology) found the variant in the gene for lipoprotein(a), a cholesterol-rich particle that circulates in the blood. CHARGE oversees genomic studies of five large study populations in the United States and Europe, including the (FHS), which is a part of the National Heart, Lung, (NHLBI) at the National Institutes of Health.  

The findings will be published in the Feb. 7 issue of The New England Journal of Medicine.  

“No medications tested to date have shown an ability to prevent or even slow progression of aortic stenosis, and treatments are limited beyond the major step of replacing the aortic valve,” said study co-author Christopher O’Donnell, M.D., M.P.H., senior director for genome research at the NHLBI and associate director of the FHS. “By identifying for the first time a common genetic link to aortic stenosis, we might be able to open up new therapeutic options.”  

The CHARGE researchers conducted a genome-wide analysis of 2.5 million known genetic variants in a group of nearly 7,000 white participants. The analysis identified a variant in the lipoprotein(a), or Lp(a), gene that was highly correlated with calcification of the aortic valve, as measured by computed tomography (CT) scanning. Follow-up analysis in more than 6,000 additional participants, including Hispanics, African-Americans, and Chinese-Americans, confirmed this correlation. The variant was present in about 7 percent of the study population and the people who carry it generally had higher amounts of Lp(a) circulating in their blood. The function of Lp(a) is unknown, but it is associated with an elevated risk of heart disease.  

Another independent analysis carried out by CHARGE followed participants in Sweden and Denmark, and found that people with the Lp(a) variant had higher risks of clinical heart valve disease and of needing valve replacement surgery.  

“What makes these findings provocative is that we linked the genetic variant with a physiological change in lipoprotein levels, disease precursor in the form of calcium buildup, and fully diagnosed , across multiple ethnicities,” O’Donnell said. “The study suggests a causal relation between Lp(a) and , but further work will be needed to see whether medications that lower Lp(a) levels can lower the risk or slow the development of valve disease.”  

In addition to the FHS, this work included data from the NHLBI’s Multi-Ethnic Study of Atherosclerosis, the Age Gene/Environment Susceptibility Study, the Heinz Nixdorf Recall Study, the Malmo Diet and Cancer Study, and the Copenhagen City Heart Study.


Source: The National Heart, Lung, and Blood Institute (NHLBI)