Ané Jobse1, Marlien Pieters2, Cornelie Nienaber-Rousseau1, Hendriek Boshuizen3, Tiny Hoekstra4, Moniek P M de Maat5. 1. Centre of Excellence for Nutrition, North-West University, Potchefstroom, North West, South Africa. 2. Centre of Excellence for Nutrition, North-West University, Potchefstroom, North West, South Africa. Electronic address: marlien.pieters@nwu.ac.za. 3. Department of Human Nutrition, Wageningen University and Research Centre, Wageningen, the Netherlands. 4. Centre of Excellence for Nutrition, North-West University, Potchefstroom, North West, South Africa; Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands. 5. Department of Hematology, Erasmus University Medical Centre, Rotterdam, the Netherlands.
Abstract
INTRODUCTION: Increased fibrinogen is associated with cardiovascular disease risk. It is, however, not known to what extend environmental and genetic factors and/or their interaction influence changes in total and γ' fibrinogen over time. We aimed to determine how variation within the fibrinogen gene as well as environmental factors influence the change in total and γ' fibrinogen over time, and also whether gene-environment interactions influence total and γ' fibrinogen on a cross-sectional and prospective level in Africans. MATERIALS AND METHODS: This prospective study consisted of 2010 participants at baseline and 1288 participants at follow-up (5 years). RESULTS: The gene-environment interactions that were associated with fibrinogen concentration on a cross-sectional level were: FGA 2224 G>A (rs2070011) with age (p=0.005), FGB Arg448Lys (rs4220) with HIV status (p<0.0001) and FGB 1038 G>A (rs1800791) with HbA1c (p=0.01). The only factor that independently influenced the change in total fibrinogen levels over time, was baseline CRP (p<0.0001) and FGG 10034 C>T (rs2066865) was the only single nucleotide polymorphism that independently influenced the change in fibrinogen γ' levels over time (p=0.02). Only the FGG 9340 T>C (rs1049636) with HbA1c interaction was found to predict change in total fibrinogen concentrations over time (p=0.005). CONCLUSIONS: Gene-environment interactions influenced fibrinogen levels cross-sectionally and also mediated changes in levels over time.
INTRODUCTION: Increased fibrinogen is associated with cardiovascular disease risk. It is, however, not known to what extend environmental and genetic factors and/or their interaction influence changes in total and γ' fibrinogen over time. We aimed to determine how variation within the fibrinogen gene as well as environmental factors influence the change in total and γ' fibrinogen over time, and also whether gene-environment interactions influence total and γ' fibrinogen on a cross-sectional and prospective level in Africans. MATERIALS AND METHODS: This prospective study consisted of 2010 participants at baseline and 1288 participants at follow-up (5 years). RESULTS: The gene-environment interactions that were associated with fibrinogen concentration on a cross-sectional level were: FGA 2224 G>A (rs2070011) with age (p=0.005), FGB Arg448Lys (rs4220) with HIV status (p<0.0001) and FGB 1038 G>A (rs1800791) with HbA1c (p=0.01). The only factor that independently influenced the change in total fibrinogen levels over time, was baseline CRP (p<0.0001) and FGG 10034 C>T (rs2066865) was the only single nucleotide polymorphism that independently influenced the change in fibrinogen γ' levels over time (p=0.02). Only the FGG 9340 T>C (rs1049636) with HbA1c interaction was found to predict change in total fibrinogen concentrations over time (p=0.005). CONCLUSIONS: Gene-environment interactions influenced fibrinogen levels cross-sectionally and also mediated changes in levels over time.