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 language | English (US) |
|---|---|
| Pages (from-to) | 1489-1492 |
| Number of pages | 4 |
| Journal | Arteriosclerosis, Thrombosis, and Vascular Biology |
| Volume | 25 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 2005 |
| Externally published | Yes |
Fingerprint
Keywords
- Association
- Heritability
- Linkage
- TFPI
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
A locus on chromosome 2 influences levels of tissue factor pathway inhibitor : Results from the GAIT study. / 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.
In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 25, No. 7, 07.2005, p. 1489-1492.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A locus on chromosome 2 influences levels of tissue factor pathway inhibitor
T2 - Results from the GAIT study
AU - Almasy, L.
AU - Soria, J. M.
AU - Souto, J. C.
AU - Warren, D. M.
AU - Buil, A.
AU - Borrell, M.
AU - Muñoz, X.
AU - Sala, N.
AU - Lathrop, M.
AU - Fontcuberta, J.
AU - Blangero, J.
PY - 2005/7
Y1 - 2005/7
N2 - 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.
AB - 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.
KW - Association
KW - Heritability
KW - Linkage
KW - TFPI
UR - http://www.scopus.com/inward/record.url?scp=21544443131&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=21544443131&partnerID=8YFLogxK
U2 - 10.1161/01.ATV.0000166602.04711.2e
DO - 10.1161/01.ATV.0000166602.04711.2e
M3 - Article
VL - 25
SP - 1489
EP - 1492
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 7
ER -