Genes account for roughly 40-60% of the risk for developing Coronary Artery Disease (CAD).[1] Genetic studies have helped clarify the causes of atherosclerotic heart disease like Coronary Artery Disease for decades. The way LDL particles are made and the role they play in causing atherosclerosis, for example, were uncovered from early studies on people with genetically raised cholesterol levels.[2]
Familial hypercholesterolemia (“FH”) is a condition in which a collection of different genetic variants cause elevated LDL cholesterol levels in the blood. [3] Having a non-functional gene that codes for either Apolipoprotein B (ApoB), PCSK9, or the LDL-receptor protein will raise blood LDL-C level and increases risk for atherosclerosis and Coronary Artery Disease. Having multiple variants in different genes, and especially having two of the same variant in the same gene, increases heart disease risk to an even greater extent.[3] Globally, about 1 in 300 people have familial hypercholesterolemia, although the prevalence can be higher or lower depending on the population (i.e., the prevalence of FH among French-Canadians is about 1 in 80; a similar estimate exists for South African Afrikaners). [4]
Another development in identifying genetic risk factors for atherosclerotic heart disease risk is recent research on the role of Lipoprotein a (LP(a), not to be confused with LPA, the gene encoding the LP(a) protein). LP(a) levels vary considerably between people, and the differences in levels of this lipoprotein have been reliably shown to determine atherosclerosis risk.[5] LP(a) levels are 80-90% determined by genetics, and elevated LP(a) levels are found in about 20% of the global population.[6]
Genetic variants in inflammation-regulation pathways (i.e., 5′-lipoxygenase) also appear to affect the risk for atherosclerosis and Coronary Artery Disease.[7]
References
- ^Roberts R, Stewart AFGenes and coronary artery disease: where are we?J Am Coll Cardiol.(2012-Oct-30)
- ^Brown MS, Goldstein JLReceptor-mediated control of cholesterol metabolism.Science.(1976-Jan-16)
- ^Ison HE, Clarke SL, Knowles JWFamilial HypercholesterolemiaGeneReviews.(2014-01)
- ^Brunham LR, Hegele RAWhat Is the Prevalence of Familial Hypercholesterolemia?ATVB.(2021 Aug)
- ^Nordestgaard BG, Langsted ALipoprotein (a) as a cause of cardiovascular disease: insights from epidemiology, genetics, and biology.J Lipid Res.(2016-11)
- ^Wilson DP, Jacobson TA, Jones PH, Koschinsky ML, McNeal CJ, Nordestgaard BG, Orringer CEUse of Lipoprotein(a) in clinical practice: A biomarker whose time has come. A scientific statement from the National Lipid Association.J Clin Lipidol.(2019)
- ^Tsai AK, Li N, Hanson NQ, Tsai MY, Tang WAssociations of genetic polymorphisms of arachidonate 5-lipoxygenase-activating protein with risk of coronary artery disease in a European-American population.Atherosclerosis.(2009-Dec)