A Genome Search for Genetic Determinants That Influence Plasma Fibrinogen Levels

Abstract

Background— Fibrinogen levels are a widely accepted risk factor for cardiovascular disease, but the extent of the genetic component is unknown. Materials and Results— To search for these genes, we conducted a genome-wide scan using 21 Spanish families from the Genetic Analysis of Idiopathic Thrombophila (GAIT) Project. Two loci were detected: 1 on chromosome 12 and another on chromosome 14. There are no cardiovascular-related candidate genes on chromosome 14, which implies that this locus represents a novel cardiovascular risk factor. Importantly, the locus on chromosome 12 contains the hepatocyte nuclear factors (TCF1), a candidate gene involved in the hepatocyte-specific transcription of the fibrinogen α-chain and β -chain genes. Three polymorphisms in TCF1 showed significant association with fibrinogen levels, supporting the implication of TCF1 in the determination of this phenotype. Conclusions— Two loci , 1 on chromosome 12 (most likely the TCF1 ) and another on chromosome 14, are important determinants of fibrinogen levels in Spanish families. These data should help define the relationship between fibrinogen levels and the risk of cardiovascular disease.