Skip to main content
Premium Trial:

Request an Annual Quote

Genetic Study Supports Potential Lipid Role in Aortic Cardiovascular Condition

NEW YORK (GenomeWeb) – A new study suggests genetic risk variants that affect blood lipid levels may offer clues to an individual's risk of developing a cardiovascular disease called abdominal aortic aneurysm (AAA), an enlargement affecting the large artery carrying blood from the heart that may lead to ruptures and death.

For a study published today in JAMA Cardiology, members of an international team led by investigators from the University of Cambridge used Mendelian randomization to look at relationships between lipid associated SNPs, blood lipid levels, and AAA risk in nearly 53,000 AAA cases or controls. They noted that individuals with genetic variants predicted to raise low-density lipoprotein cholesterol (LDL-C) levels were at slightly higher odds of developing AAA, as were those with higher predicted triglyceride levels.

On the other hand, the team reported, individuals who had variants implicated in higher-than usual high-density lipoprotein cholesterol (HDL-C) levels appeared to be at somewhat reduced risk for AAA.

Specific variants with ties to LDL-C or HDL-C levels supported these broad patterns as well, prompting the authors to argue that "the major lipid fractions — LDL-C, HDL-C, and [triglycerides] — are likely to play important roles in the etiology of AAA." They also noted that "consideration should be given to measures aimed at targeting lipids to reduce risk of AAA, using established and emerging therapies."

For their analysis, the researchers focused on genotyping profiles at 180 lipid-associated SNPs in as many as 4,914 individuals with AAA and 48,002 unaffected controls from five prior genome-wide association studies involving cohorts from the UK and Australia, New Zealand, the US, the Netherlands, and Iceland.

Their Mendelian randomization analysis indicated that genetic risk scores associated with a one standard-deviation rise in LDL-C was associated with a roughly 1.7-fold uptick in AAA over baseline risk, as was a comparable predicted increase in triglycerides. When it came to HDL-C, genetic risk scores associated with a one standard deviation increase were linked to an apparent decline in AAA risk. In that group, AAA was about one-third less common than usual.

The researchers also considered potential AAA impacts for lipid-linked variants in genes related to the functions of statin, CETP inhibitor, and PCSK9 inhibitor drugs. In the case of HMGCR, a genetic stand-in for statins, they found that a variant implicated in decreased LDL-C levels was associated with a slight decline in AAA risk. For CETP, a gene used to get a glimpse at CETP inhibitor activity, a variant implicated in enhanced HDL-C levels also seemed to notch down an individual's odds of developing AAA.

An LDL-C-lowering variant in the PCSK9 gene did not appear to prompt a decrease in AAA risk, though the researchers noted that a recent phase 3 clinical trial pointed to possible cardiovascular disease mitigation by PCSK9 inhibitors, hinting that it may still be worth exploring such therapies in AAA prevention. 

The authors cautioned that "these genetic analyses do not provide definitive evidence" of a causal role for lipids in AAA pathogenesis. Still, they wrote, "the burden of genetically influenced dyslipidemia in patients with AAA is considerable, and by extrapolation, these [Mendelian randomization] analyses lend support to the lipids playing an important role in AAA etiology and thus targeting lipids through pharmacological modification in patients with small AAAs may well be justified."

The Scan

Genetic Ancestry of South America's Indigenous Mapuche Traced

Researchers in Current Biology analyzed genome-wide data from more than five dozen Mapuche individuals to better understand their genetic history.

Study Finds Variants Linked to Diverticular Disease, Presents Polygenic Score

A new study in Cell Genomics reports on more than 150 genetic variants associated with risk of diverticular disease.

Mild, Severe Psoriasis Marked by Different Molecular Features, Spatial Transcriptomic Analysis Finds

A spatial transcriptomics paper in Science Immunology finds differences in cell and signaling pathway activity between mild and severe psoriasis.

ChatGPT Does As Well As Humans Answering Genetics Questions, Study Finds

Researchers in the European Journal of Human Genetics had ChatGPT answer genetics-related questions, finding it was about 68 percent accurate, but sometimes gave different answers to the same question.