A Genome Search for Genetic Determinants That Influence Plasma Fibrinogen Levels

Abstract number: P1974

Soria¹ JM, Almasy² L, Souto¹ JC, Buil¹ A, Lathrop³ M, Blangero² J, Fontcuberta¹ J

¹¹Unitat d'Hemostàsia i Trombosi. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain ¹¹Unitat d'Hemostàsia i Trombosi. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain ²²Southwest Foundation for Biomedical Research, San Antonio, TX, USA ³³Centre National de Genotypage, Evry, France

Background:  Fibrinogen levels are a widely accepted risk factor for cardiovascular disease, but the extent of the genetic component is unknown.

Material and results:  To search for these genes, we conducted a genome-wide scan using 21 Spanish families from the GAIT Project. Two loci were detected, one 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 a candidate gene (TCF1) involved in the hepatocyte-specific transcription of the fibrinogen alpha and beta chain genes. Three polymorphisms in TCF1 showed significant association with fibrinogen levels, supporting the implication of the TCF1 in the determination of this phenotype. It interesting that the chromosome 4 region, where the fibrinogen genes are located, showed weak evidence of linkage, indicating these genes play a minor role in the normal variation of fibrinogen levels.

Conclusions:  Two loci, one 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 to define the relationship between fibrinogen levels and the risk of cardiovascular disease.