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  • Title: A locus on chromosome 2 influences levels of tissue factor pathway inhibitor: results from the GAIT study.
    Author: Almasy L, Soria JM, Souto JC, Warren DM, Buil A, Borrell M, Muñoz X, Sala N, Lathrop M, Fontcuberta J, Blangero J.
    Journal: Arterioscler Thromb Vasc Biol; 2005 Jul; 25(7):1489-92. PubMed ID: 15845911.
    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. CONCLUSIONS: These results suggest that polymorphisms in and around the TFPI structural gene may be the major genetic determinants of variation in TFPI levels.
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