Cardiovascular disease genetics: a long and winding road.
OBJECTIVE
This review has two major goals. The first goal is to raise some of the methodological problems associated with studying the genetics of complex disorders, specifically cardiovascular diseases. The second is to update the reader with the most recent findings in the area of genotype-phenotype associations as well as the interaction between genetic factors and cardiovascular disease risk markers, with emphasis on those related to lipid metabolism.


RESULTS
In terms of new information, three topics are presented: (1) new findings related to classical candidate genes, such as apolipoprotein E, cholesteryl ester transfer protein and hepatic lipase; (2) recent reports related to new loci that have joined the growing list of cardiovascular disease candidate genes (i.e. ATP-binding cassette transporters A1 and C6, peroxisome proliferator activated receptor alpha, interleukin-6); and (3) studies showing that multiple genes appear to be at the intersection of several age-related disorders such as cardiovascular disease, neurological disorders and osteoporosis (i.e. apolipoprotein E, vitamin D receptor, matrix Gla protein, peroxisome proliferator activated receptor gamma, angiotensin-converting enzyme, estrogen receptor, androgen receptor, methylenetetrahydrofolate reductase).


CONCLUSIONS
The dramatic increase in our ability to carry out genotyping is creating a tremendous wealth of information in terms of associations between genetic markers and biochemical or clinical phenotypes. Increased attention, however, should be placed on study design and replication of findings. This should also be facilitated by the inclusion of multiple markers per loci in order to provide a more precise definition of the alleles associated with the phenotypes of interest. Moreover, given the fact that most of the phenotypes are equally affected by genetic and environmental factors, studies should emphasize the analyses of their interaction.
Ordovas
Jose M
JM
Nutrition and Genomics Laboratory, Jean Mayer-USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts 02111, USA. ordovas@hnrc.tufts.edu
D002318:Cardiovascular Diseases / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D020412:Multifactorial Inheritance / Q000235:genetics; D010641:Phenotype