Familial studies on the genetics of cardiovascular diseases: The Stanislascohort

In a given individual, the level of cardiovascular risk results from the co mbination of and interactions between genetic and environmental components. We choose to investigate segregation analysis of intermediate phenotypes i n healthy nuclear families, belonging to the Stanislas cohort, a large fami lial cohort composed of 1006 families, which will be followed for 10 years. We developed a panel of 35 genetic markers including genes involved in lip id metabolism, regulation of blood pressure, thrombosis, platelet function, and endothelial cell adhesion. The allele frequencies of the studied polym orphisms were in agreement with those reported in other Caucasian populatio ns. As an example of segregation analysis, we investigated carotid intima-m edia thickness (CIMT) variability in a subset sample of the Stanislas cohor t. We found that about 30% of CIMT variability was attributable to genetic factors. Associations between CIMT and polymorphisms in apo CIII, cholester yl ester transfer protein, methylene tetrahydrofolate reductase, and fibrin ogen genes were observed and explained about 20% of CIMT variability in men . Furthermore, as another example of association studies, we investigated t he relations between E-selectin polymorphisms and blood pressure interindiv idual variability and longitudinal changes in unrelated adults of this fami lial population. The E-selectin Phe(554) allele was found associated with l ower systolic blood pressure and diastolic blood pressure.