Lipid associated variant linked to aortic stenosis, valve disorders

Published on February 11, 2013 at 5:15 PM · No Comments

By Helen Albert, Senior medwireNews Reporter

medwireNews: People who carry a lipoprotein(a) gene (LPA) variant are at increased risk for aortic valve calcification and aortic stenosis, suggest study findings.

The team showed that individuals with one or more copies of the G (minor) allele of the LPA single nucleotide polymorphism (SNP) rs10455872 also have higher lipoprotein(a) levels than noncarriers - suggesting a causal role in their development of the condition.

"This is an important step forward in understanding the biology of the development of aortic stenosis and how this common genetic variant, which is found in thirteen per cent of the general population, contributes to that risk," commented senior author Wendy Post (Johns Hopkins University School of Medicine, Baltimore, Maryland, USA) in a press statement.

"Advancing age is a major risk factor for aortic stenosis and, with the aging population this will become an even bigger health concern," she added.

Post and team carried out a genome-wide association study to search for SNPs associated with aortic-valve calcification (in 6942 people) and mitral-annular calcification (in 3795 people) among individuals of White European descent participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium.

They found that the LPA SNP rs10455872 was significantly associated with aortic-valve calcification in initial and replication White European, African-American, and Hispanic-American cohorts. More specifically, the risk for aortic-valve calcification increased 2.05-fold for each copy of the G-allele carried.

In two cohorts that assessed levels of lipoprotein(a), there was also a significant association with the G-allele of rs10455872 with carriers having higher levels. The team estimated that the risk for aortic-valve calcification increased by 62% per log unit increase in lipoprotein(a) levels.

Further analysis in a Swedish cohort showed that the same SNP is also significantly associated with incident aortic stenosis and aortic-valve replacement, increasing the risks per G-allele carried 1.68 and 1.54 fold, respectively. This association was replicated in an independent Danish cohort.

Regarding mitral-annular calcification, two SNPs (rs17659543 and rs13415097) near the IL1F9 gene had genome wide significance in the initial investigation, but this association was not consistently replicated.

"Further studies are needed to evaluate whether lowering lipoprotein(a) levels will reduce the incidence or progression of aortic-valve disease," conclude the authors in the New England Journal of Medicine.

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