Lipoproteinstoffwechsel und koronare Herzkrankheit

A better understanding of complex diseases and their genetics has been gained by investigating genetic disorders of lipoprotein metabolism. This has resulted in the development of ddrugs to prevent atherosclerosis, the most frequent cause of death in industrialized countries. Thus, analysis of familial hypercholesterinemia (FH), the most frequent cause of which are mutations on the LDLR gene, has contributed to the development of HMG-CoA reductase inhibitors (statins). Meanwhile, in genome-wide association studies (GWAS), variants in over 90 genes have been found to influence the concentration of plasma lipids. However, these explain only a small fraction of the genetic variance of the traits. Taking the classical polymorphism of Apo-E as an example, it is discussed that one possible reason for the ??missing heritability?? may be the selection of the SNPs on the arrays used in the GWAS. Further, this polymorphism demonstrates how interactions may mask a connection between a genotype and a disease. Genetic studies based on the principle of ??Mendelian randomization?? have established the causal role of a high Lp(a) concentration as a risk factor for coronary heart disease (CHD). For patients with end-stage renal disease, however, a polymorphism (KIV-2 CNV) is a better predictor for CHD than Lp(a) concentration.