Key result
Genome-wide scan links 2 novel loci and TCF1 variants to plasma fibrinogen levels.
Observational
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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 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.
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Soria et al. (2005) conducted an observational in Idiopathic thrombophilia and cardiovascular disease risk. Genetic loci on chromosomes 12 (including TCF1 polymorphisms) and 14 was evaluated on Plasma fibrinogen levels. A genome-wide scan in 21 Spanish families identified 2 loci (chromosomes 12 and 14) and 3 TCF1 polymorphisms significantly associated with plasma fibrinogen levels.
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