on March 10, 2005
Published online before print March 10, 2005, doi: 10.1161/01.ATV.0000161927.38739.6f
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Submitted on October 14, 2004
Accepted on February 18, 2005
A Genome Search for Genetic Determinants That Influence Plasma Fibrinogen Levels
José Manuel Soria *;
From the Unitat d’Hemostàsia i Trombosi (J.M.S., J.C.S., A.B., J.F.), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Southwest Foundation for Biomedical Research (L.A., J.B.), San Antonio, Tex; and Centre National de Genotypage (M.L.), Evry, France.
* To whom correspondence should be addressed. E-mail: jsoria{at}hsp.santpau.es.
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 a candidate gene (TCF1) involved in the hepatocyte-specific transcription of the fibrinogen 
-chain and 
-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.
Key words: thrombosis • quantitative trait locus • GAIT Project • fibrinogen and TCF1 gene
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