Protein C levels are regulated by a quantitative trait locus on chromosome 16: Results from the Genetic Analysis of Idiopathic Thrombophilia (GAIT) Project

Alfonso Buil, José Manuel Soria, Juan Carlos Souto, Laura Almasy, Mark Lathrop, John Blangero, Jordi Fontcuberta

    Research output: Contribution to journalArticle

    29 Scopus citations

    Abstract

    Objective-Protein C (PC) is a component of the protein C anticoagulant pathway. PC deficiency is a risk factor associated with venous thromboembolism. As part of the Genetic Analysis of Idiopathic Thrombophilia (GAIT) Project, we conducted a genome-wide linkage scan to localize genes that influence variation in PC plasma levels. Methods and Results-PC levels were measured in 398 individuals belonging to 21 Spanish families. A total of 485 DNA microsatellite markers were genotyped to provide a 7.1-cM genetic map. Variance component linkage methods were used to evaluate linkage and to detect quantitative trait loci (QTL). A region on chromosome 16 (16q23), flanked by markers D16S3106 and D16S516, showed strong evidence of linkage with PC levels (LOD = 3.69). This region contains 1 positional candidate gene, the NAD(P)H:dehydrogenase quinone 1 (NQO1), involved in vitamin K metabolism. The association of 1 SNP of this gene with PC levels (P=0.005) strongly supports the implication of NQO1 gene in the variability of PC levels. Conclusions-These results illustrate the application of genomic scans to identify the genetic determinants of quantitative variation in a component of the hemostatic pathways. They provide strong evidence for a locus (QTL) on chromosome 16 that influences PC levels.

    Original languageEnglish (US)
    Pages (from-to)1321-1325
    Number of pages5
    JournalArteriosclerosis, Thrombosis, and Vascular Biology
    Volume24
    Issue number7
    DOIs
    StatePublished - Jul 2004

    Keywords

    • Linkage analysis
    • NQO1 gene
    • Protein C
    • Quantitative trait locus
    • Variance components

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

    Fingerprint Dive into the research topics of 'Protein C levels are regulated by a quantitative trait locus on chromosome 16: Results from the Genetic Analysis of Idiopathic Thrombophilia (GAIT) Project'. Together they form a unique fingerprint.

  • Cite this