Faculty Collaboration Database

Fibrinogen alpha and gamma genes and factor VLeiden in children with thromboembolism: results from 2 family-based association studies. Blood 2009 Aug 27;114(9):1947-53

Date

06/12/2009

Pubmed ID

19515723

DOI

10.1182/blood-2009-04-218727

Scopus ID

2-s2.0-70349249995 (requires institutional sign-in at Scopus site)   31 Citations

Abstract

Previous case-control studies showed that genetic variation in the fibrinogen gamma gene (FGG) increased the risk for deep vein thrombosis (VT) in adults. We investigated the association between the fibrinogen alpha (FGA) and FGG haplotypes, the factor V(Leiden)-mutation, and pediatric VT and thromboembolic stroke (TS) in 2 independent study samples. Association analysis revealed that the FGA-H1 and FGG-H2 haplotypes were significantly overtransmitted to VT patients (FGA-H1, P = .05; FGG: H2, P = .032). In contrast, the FGG-H3 haplotype was undertransmitted (P = .022). In an independent study sample, FGA-H1 (P = .008) and FGG-H2 (P = .05) were significantly associated with TS. The association of FGA and FGG haplotypes with VT was more pronounced in FV(Leiden)-negative families (FGA-H1, P = .001; FGG-H2, P = .001), indicating a genetic interaction between both risk factors. The risk-conferring FGG-H2 and the protective FGG-H3 haplotypes correlated with low (FGG-H2) and high (FGG-H3) levels of the gamma' chain variant, respectively. These results provide independent and novel evidence that FGA-H1 and FGG-H2 variants are associated with an increased risk of VT and TS in children. The observed negative correlation of genetic VT risk with the plasma levels of the fibrinogen gamma' variant suggests that FGG-H2 and -H3 haplotypes modify thrombosis risk by controlling the level of this FGG splice isoform.

Author List

Nowak-Göttl U, Weiler H, Hernandez I, Thedieck S, Seehafer T, Schulte T, Stoll M

MESH terms used to index this publication - Major topics in bold

Adolescent
Case-Control Studies
Child
Child, Preschool
Cohort Studies
Factor V
Family Health
Female
Fibrinogen
Fibrinogens, Abnormal
Humans
Infant
Male
Thromboembolism
Thrombosis
Venous Thrombosis