Genetic profiling in healthy subjects from the Stanislas cohort based on 24 polymorphisms: effects on biological variables

Background: The association of genetic profiles with biological or clinical assessments is not clearly established especially among apparently healthy subjects. Methods: A multivariate statistical analysis was performed on 24 polymorphisms related to the main metabolic pathways involved in cardiovascular diseases (CVDs). They were collected among 1551 healthy subjects of the Stanislas cohort to obtain genetic profiles. Association with biological variables was then studied at baseline (t(0)) and 5 years later (t(5)). Results: Six genetic clusters were identified with relevant profiles and five polymorphisms from the selectin, apolipoprotein C3 and lipoprotein lipase genes (SELE-98G/T, APOC3-3175C/G, APOC3-482C/T, APOC3-1100C/T, LPL-93T/G) were sufficiently characteristic to associate 99.6% of the subjects with their corresponding cluster. A 5-year follow-up showed that clinical and biological measurements in relation to CVD risk factors already differ with triglyceride (p=0.009 for t(0) and p=0.005 for t(5)) and high-density lipoprotein cholesterol (p=0.014 for t(0), and p=0.003 for t(5)) for these previous genetic clusters. Conclusions: This study presents the hypothesis that SELE could be protective, whereas APOC3 could be associated with risk. It remains to be seen whether these polymorphisms will be predictive of CVD events among the selected clusters of different metabolic subtypes after a 10-year follow-up.