title: 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.
  
  
  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.affiliation: Southwest Foundation for Biomedical Research, San Antonio, Tex X 78245-0549, USA. almasy@darwin.sfbr.org
authors.forename: L
authors.initials: L
authors.lastname: Almasy
authors.forename: J M
authors.initials: JM
authors.lastname: Soria
authors.forename: J C
authors.initials: JC
authors.lastname: Souto
authors.forename: D M
authors.initials: DM
authors.lastname: Warren
authors.forename: A
authors.initials: A
authors.lastname: Buil
authors.forename: M
authors.initials: M
authors.lastname: Borrell
authors.forename: X
authors.initials: X
authors.lastname: Muñoz
authors.forename: N
authors.initials: N
authors.lastname: Sala
authors.forename: M
authors.initials: M
authors.lastname: Lathrop
authors.forename: J
authors.initials: J
authors.lastname: Fontcuberta
authors.forename: J
authors.initials: J
authors.lastname: Blangero
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D002889:Chromosomes, Human, Pair 2; D005260:Female; D023281:Genomics; D006801:Humans; D007223:Infant; D008074:Lipoproteins / Q000097:blood* / Q000235:genetics*; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013927:Thrombosis / Q000097:blood* / Q000235:genetics*
chemical_list: D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor