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Isolation and Analysis of Plasma Lipoproteins by Ultracentrifugation
Published on: January 28, 2021
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Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart
Tom G Richardson1,2, Eleanor Sanderson1,2, Tom M Palmer1,2
1Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
Plos Medicine
|March 24, 2020
Summary
Apolipoprotein B is the primary driver of coronary heart disease (CHD) risk among lipoprotein lipids. This study used Mendelian randomization to identify apolipoprotein B as the key causal factor, distinct from LDL cholesterol and triglycerides.
Area of Science:
- Cardiovascular Genetics
- Lipid Metabolism
- Epidemiology
Background:
- Circulating lipoprotein lipids are established causes of coronary heart disease (CHD).
- The specific causal roles of individual lipoprotein lipid traits in CHD etiology remain incompletely understood.
- Multivariable Mendelian randomization (MR) is employed to dissect these complex relationships.
Purpose of the Study:
- To compare the causal roles of various lipoprotein lipid traits in the etiology of coronary heart disease (CHD).
- To identify the predominant lipoprotein lipid-related entity responsible for CHD risk.
- To leverage genetic instruments for robust causal inference.
Main Methods:
- Genome-wide association studies (GWAS) were conducted on lipoprotein lipid traits in the UK Biobank.
- Single nucleotide polymorphisms (SNPs) associated with LDL cholesterol, triglycerides, apolipoprotein B, HDL cholesterol, and apolipoprotein A-I were identified.
- Univariable and multivariable Mendelian randomization (MR) analyses were performed using CHD case data from CARDIoGRAMplusC4D.
Main Results:
- Individually, higher levels of LDL cholesterol, triglycerides, and apolipoprotein B were associated with increased CHD risk.
- In multivariable MR analyses, only apolipoprotein B retained a significant causal effect on CHD risk.
- Estimates for LDL cholesterol and triglycerides were attenuated or reversed when accounting for apolipoprotein B.
- Higher HDL cholesterol and apolipoprotein A-I showed protective effects individually, but these were nullified when considering apolipoprotein B.
Conclusions:
- Apolipoprotein B emerges as the predominant lipoprotein lipid trait causally linked to coronary heart disease (CHD) risk.
- These findings highlight apolipoprotein B as a critical therapeutic target for CHD prevention.
- Understanding the distinct causal pathways of lipoprotein lipids is crucial for refining cardiovascular risk assessment.
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