A genome search for genetic determinants that influence plasma fibrinogen levels.
BACKGROUND
Fibrinogen levels are a widely accepted risk factor for cardiovascular disease, but the extent of the genetic component is unknown.


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 alpha-chain and beta-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.
Soria
José Manuel
JM
Unitat d'Hemostàsia i Trombosi, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. jsoria@hsp.santpau.es
Almasy
Laura
L
Souto
Juan Carlos
JC
Buil
Alfonso
A
Lathrop
Mark
M
Blangero
John
J
Fontcuberta
Jordi
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005260:Female; D005340:Fibrinogen / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D023281:Genomics; D006239:Haplotypes; D006801:Humans; D007223:Infant; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000453:epidemiology / Q000235:genetics*
D005340:Fibrinogen