How do genetics influence low-density lipoprotein cholesterol (LDLc) levels?

Updated: Apr 09, 2021
  • Author: Nainesh K Gandhi, MD, MSE; Chief Editor: Keith K Vaux, MD  more...
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Answer

Low-density lipoprotein cholesterol (LDLc) is well established as a key causal factor in the development of atherosclerotic vascular disease, especially coronary heart disease (CHD). Although there is wide variability of LDLc levels within the population, several studies have demonstrated that LDLc levels in related individuals tend to be similar, indicating that the LDLc level is a heritable trait. [1, 2, 3, 4, 5, 6, 7] Because of these findings, there has been considerable investigation into the genetics that determine the LDLc plasma concentration, which is part of the larger effort to improve the risk assessment of future cardiovascular disease in any given person. [8]  Because of these findings, there has been considerable investigation into the genetics that determine the LDLc plasma concentration, which is part of the larger effort to improve the risk assessment of future cardiovascular disease in any given person.

The genetics of LDLc can be divided into 2 main groups: one where a clear pattern of inheritance (mendelian) is evident, and the other where an inheritance pattern is not easily deciphered. The syndrome of familial hypercholesterolemia (FH) falls into the first group, where clear single variant mutations that are inherited in a mendelian fashion (autosomal recessive or dominant pattern) profoundly alter the LDLc level. This is in contrast to other individuals with the FH phenotype, with no clear single gene mutation that can explain the alteration in LDLc. This is likely the more common scenario, in which there may be a collection of gene variants (single-nucleotide polymorphisms, or SNPs) that, together with traditional dietary and lifestyle factors, exert a compound effect similar to the classic gene mutations of FH.


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