Fibrinogen and CRP in Israeli families: Genetic and environmental sources of concentrations and longitudinal changes

Objective: To estimate the genetic and environmental determinants of plasma fibrinogen and C-reactive protein (CRP). Methods and results: A complex segregation analysis was undertaken in a sample of 142 kindreds residing in Kibbutz settlements in Israel. In addition, included in this analysis were family members who were examined 10 years earlier in the framework of this study. Analysis indicated a major locus in addition to polygenic effect that explained the sex- and age-adjusted levels and longitudinal changes in plasma fibrinogen. A non-transmitted environmental major factor with no polygenic effect explained the adjusted variation in levels and change of CRP. Both the particular genotypes determined by the major genetic factor associated with fibrinogen levels and the particular ousiotypes determined by the major environmental factor associated with CRP levels were sex- and age-dependent. In addition, our results demonstrated significant interactions between polygenotype and gender, age and environmental factors such as smoking and BMI on fibrinogen and CRP levels. Conclusions: Our models that consider interactions between genotypes and gender, age and environmental exposures have the potential to improve our understanding of the genetics of fibrinogen and CRP levels.