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

Research output: Contribution to journalArticlepeer-review

20 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 2005
Externally publishedYes

Keywords

  • Association
  • Heritability
  • Linkage
  • TFPI

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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