A locus on chromosome 2 influences levels of tissue factor pathway inhibitor: Results from the GAIT study

L. Almasy, J. M. Soria, J. C. Souto, D. M. Warren, A. Buil, M. Borrell, X. Muñoz, N. Sala, M. Lathrop, J. Fontcuberta, J. Blangero

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    19 Scopus citations

    Abstract

    Objective-Levels of tissue factor pathway inhibitor (TFPI) have been associated with arteriosclerosis and thrombotic disease. Although a genetic component to variation in TFPI levels is well-documented, no systematic genome-wide screens have been conducted to localize genes influencing levels of TFPI. Methods and Results-We studied TFPI levels in 397 individuals in 21 Spanish families participating in the Genetic Analysis of Idiopathic Thrombosis (GAIT) study. Twelve families were selected through a proband with idiopathic thrombosis and 9 were ascertained without regard to phenotype. A genome scan was performed using microsatellite markers spaced at approximately 10 cM intervals. Standard multipoint variance component linkage methods were used. The heritability of TFPI levels was 0.52 (P<0.0001), with no evidence for shared household effects. In the genome screen, only 1 LOD score >2 was observed. On chromosome 2q, the maximum multipoint LOD score was 3.52 near marker D2S1384. This is near the structural gene for TFPI, which is located at 2q32. In follow-up association analyses, marginal evidence of association (P=0.04) was observed with the TFPI promoter variant C-399T. Conclusion-These results suggest that polymorphisms in and around the TFPI structural gene may be the major genetic determinants of variation in TFPI levels.

    Original languageEnglish (US)
    Pages (from-to)1489-1492
    Number of pages4
    JournalArteriosclerosis, Thrombosis, and Vascular Biology
    Volume25
    Issue number7
    DOIs
    StatePublished - Jul 1 2005

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    Keywords

    • Association
    • Heritability
    • Linkage
    • TFPI

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

    Cite this

    Almasy, L., Soria, J. M., Souto, J. C., Warren, D. M., Buil, A., Borrell, M., Muñoz, X., Sala, N., Lathrop, M., Fontcuberta, J., & Blangero, J. (2005). A locus on chromosome 2 influences levels of tissue factor pathway inhibitor: Results from the GAIT study. Arteriosclerosis, Thrombosis, and Vascular Biology, 25(7), 1489-1492. https://doi.org/10.1161/01.ATV.0000166602.04711.2e