Multilocus approach to cardiovascular risk

Until now, our familial studies have showed that shared genetic and environ mental factors are involved on lipid parameters variability. More precisely , being working on 119 families we have showed that: a) The apolipoprotein E (apo E) common polymorphism is involved in the total cholesterol, low den sity lipoprotein cholesterol (LDL-Chol), apo E, apo B levels variability, b ) the apolipoprotein A-IV gene had no effect on lipid metabolism parameters variability, apo A-IV levels included, c) the apolipoprotein B gene was as sociated with total cholesterol, high density lipoprotein cholesterol, LDL- Chol, triglycerides and apo B levels genetic variability, d) the lipoprotei ne lipase (LPL) gene was responsible for 6.5 % of the triglycerides variabi lity, e) the apo E and LPL 447 polymorphisms influence in conjunction lipid parameters. These preliminary results on effects and combination effects o f polymorphic genes show the interest of a multilocus approach. We have used in a subgroup of 416 individuals of a familial cohort (Stanisl as Cohort) a prototype assay that genotypes a panel of 35 polymorphic sites on 15 candidate genes of Cardiovascular diseases. Each sample is amplified by two multiplex polymerase chain reactions, then hybridized to an array o f immobilized, oligonucleotide probes. The frequencies of the rare alleles were in agreement with those reported by others in caucasian populations. T he realisation of this multiplex assay in the 1 006 families of the Stanisl as Cohort, which is underway, will allow us a better understanding of the i nterindividual variability of lipids and will contribute to the determinati on of the genetic susceptibility of one's individual to cardiovascular risk .