Analysis of the effect of multiple genetic variants of cardiovascular disease risk on insulin concentration variability in healthy adults of the STANISLAS cohort : The role of FGB -455 G/A polymorphism

Given the hypothesis of a common soil for atherosclerosis, type 2 diabetes and metabolic syndrome, we tested the contribution of gene polymorphisms involved in cardiovascular diseases on fasting insulin concentration (FIC). The polymorphisms were investigated by a multiplex assay in 308 apparently healthy French middle-aged men and women, taken from the STANISLAS cohort. FIC was measured by a microparticular enzymatic immunoassay. After a series of regression analyses involving 34 polymorphisms, FGB -455G/A was the only polymorphism that remained significantly associated with FIC when adjusting the analyses for multiple testing. Stepwise models showed that FGB polymorphism accounted for 4.39% of FIC variability in men. Additionally, interactions between FGB and with environmental factors (alcohol and smoking in men, and BMI in women) were found. To our knowledge, this is the first study reporting an influence of FGB polymorphism on FIC in a healthy population. Our results concord with the already shown link between fibrinogen concentration and FIC, and support the hypothesis of a relationship between fibrinogen and endothelium in FIC homeostasis whose alteration may induce several metabolic disorders. The contribution of this gene, although modest, is consistent with the polygenic nature of insulin levels.