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

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.

• Authors: 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
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 25 Issue 7 Pg. 1489-92 (Jul 2005) ISSN: 1524-4636 [Electronic] United States
• PMID: 15845911 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Lipoproteins
• lipoprotein-associated coagulation inhibitor

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Child
• Child, Preschool
• Chromosomes, Human, Pair 2
• Female
• Genomics
• Humans
• Infant
• Lipoproteins (blood, genetics)
• Lod Score
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Thrombosis (blood, genetics)