Genes determining cholesterol levels
Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci
Asselbergs FW et al.The American Journal of Human Genetics 2012; http://dx.doi.org/10.1016/j.ajhg.2012.08.032
Background
Both genetic and environmental factors determine cholesterol levels in the blood [1]. There is a clear relationship between abnormalities in plasma lipid levels and cardiovascular disease [2,3]. Plasma lipid and lipoprotein levels are highly heritable (40-60%)[4].Genetic associations have been studied before. In this meta-analysis, a team of international researchers analyzed approximately 50,000 genetic variants in some 2100 genes with a role in heart disease by a dense gene-centric approach. They viewed these genes in more than 65,000 people and repeated the performance in an independent survey of 25,000 people, they compared it also with previous research of another 100,000 people.
Four hospitals coordinated the large international study, called the International IBC Lipid Genetics Consortium. This consortium consists of 180 researchers worldwide, from which two from the Netherlands, UMC Utrecht and AMC Amsterdam. In addition, the Children's Hospital of Philadelphia and the Institute of Cardiovascular Sciences at University College London.
Main results
- 21 new genes were identified that affect lipid levels in the blood
- The relationship between changes in 49 newly found genes with plasma lipid levels was confirmed
Conclusion
A focused genotyping approach can further increase the understanding of heritability of plasma lipids. The newly found genes constitute a valuable target for the development of new cholesterol-lowering drugs.
References
1. Berenson, G.S., Srinivasan, S.R., Bao, W., et al. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N. Engl. J. Med. 1998:338;1650–1656.2. Arsenault, B.J., Boekholdt, S.M., and Kastelein, J.J. Lipid parameters for measuring risk of cardiovascular disease. Nat Rev Cardiol 2011: 8;197–206.
3. Di Angelantonio, E., Sarwar, N., Perry, P., et al.; Emerging Risk Factors Collaboration. Major lipids, apolipoproteins, and risk of vascular disease. JAMA 2009:302;1993–2000.
4. Weiss, L.A., Pan, L., Abney, M., Ober, C. The sexspecific genetic architecture of quantitative traits in humans. Nat. Genet. 2006:38;218–222.
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