Studying genotype-phenotype relationships: cardiovascular disease as an example.
Cardiovascular disease is a multifactorial disorder resulting from the complex interaction of a plethora of both environmental and genetic factors. The "candidate gene" approach aims at identifying the genes contributing to cardiovascular disease assessing their entire polymorphic spectrum and the consequences of their combination in appropriate large association studies. In view of the sequence data available for the entire human genome, candidate sequences will more easily be traced and located in their chromosomal context. More powerful sequencing devices are available and will hopefully give reliable and reproducible data not only on the nucleotide sequence diversity in different populations throughout candidate regions of the human genome. The choice and the assessment of disease-related or intermediate phenotypes, especially in clinical settings, will be again more crucial in the future when the knowledge of gene sequence variation significantly increases. Identification of relevant genes and genetic variants involved in the different pathophysiological steps leading to cardiovascular disease may considerably improve our understanding of the mechanisms of the disease course. This may help to identify high-risk individuals and groups or subgroups in whom specific therapeutic interventions are indicated or necessary, leading to an individually adapted clinical management.
Herrmann
Stefan-Martin
SM
Institute of Clinical Pharmacology and Toxicology, Department of Clinical Pharmacology, Benjamin Franklin Medical Center, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany. herrmann@medizin.fu-berlin.de
Paul
Martin
M
D002318:Cardiovascular Diseases / Q000235:genetics*; D005838:Genotype; D006801:Humans; D010641:Phenotype; D011110:Polymorphism, Genetic