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Approved Research

Use of a new lipid classification system for lipoprotein phenotypes to evaluate health outcomes and underlying genotypes.

Principal Investigator: Dr Anna Wolska
Approved Research ID: 97500
Approval date: February 8th 2023

Lay summary

High levels of cholesterol, particularly low-density lipoprotein-cholesterol (LDL-C), in plasma play a major role in development of cardiovascular disease (CVD). LDL-C is often called the "bad" cholesterol for this reason. Very high triglyceride (TG) levels in plasma also increase risk for cardiovascular disease. In contrast, high-density lipoprotein cholesterol (HDL-C) has gained a reputation as the "good" cholesterol since high HDL-C levels in plasma associate with decreased risk of atherosclerosis. In general, "good" cholesterol (HDL-C) resides in lipoprotein particles containing a small  protein called apoA-I whereas triglycerides and "bad" cholesterol reside in particles containing a much larger protein called apoB. These latter particles are often referred to  as "apoB-containing lipoproteins (apoB-Lps) and the cholesterol in these particles is referred to as "non-HDL-C."

apoB-Lp's come in a wide array of sizes and have different compositions, with different amounts of triglycerides and cholesterol and different types of fatty acids. Many have additional proteins bound to them besides apoB which might alter their function, making them more or less atherogenic. It is known, for example, that small dense LDL is more atherogenic than larger and less dense LDL particles, and that apoB-Lp's containing a protein called apo(a) are extremely atherogenic. In general, apoB-Lp's have been sorted into 5 classes (designated Types I - V), each leading to a characteristic phenotype, called the Fredrickson phenotypes. Due to the difficulty in measuring these 5 classes of apoB-Lps, they are not usually measured in clinical practice and their roles in health and disease have not been well-studied

Recently, our lab developed a new method to classify lipoprotein phenotypes using only plasma non-HDL-C and triglyceride levels. Hence, all traditional lipoprotein phenotypes except Type III can be determined at no extra cost using only a standard lipid panel. Additionally, we defined a new phenotype (Type VI) for patients with apoB secretion defects.

We aim to use the UK Biobank's data and our novel method of classifying lipoprotein phenotypes to determine patients' lipoprotein phenotypes and associated health outcomes and genetic mutations. The project is expected to take approximately two years. The public health impact is to improve diagnosis and to provide more personalized treatment at no extra cost to the patient.