Leaders in Pharmaceutical Business Intelligence (LPBI) Group

Lp(a) Gene Variant Association

Reporter: Larry H Bernstein, MD, FCAP

UPDATED on 2/20/2023

Lp(a) was associated with atherosclerotic cardiovascular disease (ASCVD), but whether an elevated blood level was a biomarker or a causal factor proved difficult to determine.

resurgent interest in molecular pathophysiology this past decade has clarified Lp(a)’s unique contribution to atherothrombotic disease and calcific aortic stenosis.

Lp(a) comprises an apoB particle bonded to an apo(a) particle. Apo(a) is complex and has a number of isoforms that can result in large heterogenicity in apo(a) size between, as well as within, individuals. This contributes to controversy about the ideal assay and whether Lp(a) levels should be expressed as mass (mg/dL) or number of particles (nmols/L). This should not, however, deter universal testing.

Universal Lp(a) testing would spotlight this pervasive and important risk factor that was referred to as the “horrible” cholesterol in a recent review.

To date, trials of an antisense oligonucleotide and a small interfering RNA molecule targeting hepatic LPA messenger RNA have confirmed that plasma Lp(a) levels can be significantly and safely lowered. If the ongoing Lp(a) HORIZON and OCEAN(a) phase 3 trials have positive outcomes in patients with known ASCVD, this would spawn a host of clinical trials to explore the possibilities of these therapies in primary prevention as well. These will require tens of thousands of enrollees, and universal testing would expand the pool of potential participants.

Recent data from the United Kingdom suggest that attainment of specific LDL-C levels may offset the risk for vascular events in those with high Lp(a) levels.

SOURCE

https://www.medscape.com/viewarticle/987221#vp_1

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Lp(a) Gene Variant Associated With Aortic Stenosis

Reported by Lisa Nainggolan Feb 06, 2013; GThanassoulis et al. NEJM http://www.theheart.org/article/1503525.do

People carrying this single nucleotide polymorphism (SNP) had a doubling of the risk of valve calcification on computer tomography (CT) compared with those without the variation. The same SNP has previously been identified as a risk factor for increased Lp(a) levels and coronary artery disease (CAD). Findings Could Reawaken Interest in Therapies Targeting Lp(a)

Related articles

• Genetic Study Identifies Strong Links To Aortic Valve Disease (forbes.com)
• Researchers Find Gene Variant Linked To Aortic Valve Disease (medicalnewstoday.com)
• MGH’s Largest-ever Genetic Study of Five Psychiatric Disorders: Variation in SNPs in Two Genes involved in Calcium-Channel Signaling (pharmaceuticalintelligence.com)
• Link Between Most Common Form Of Heart Valve Disease And Unusual Cholesterol (medicalnewstoday.com)

A Single Nucleotide Polymorphism is a change of a nucleotide at a single base-pair location on DNA. Created using Inkscape v0.45.1. (Photo credit: Wikipedia)