%0 Journal Article %J J Thromb Haemost %D 2008 %T Common genetic variants associated with plasma fibrin D-dimer concentration in older European- and African-American adults. %A Lange, L A %A Reiner, A P %A Carty, C L %A Jenny, N S %A Cushman, M %A Lange, E M %K Africa %K African Americans %K Aged %K Aged, 80 and over %K Blood Coagulation %K Europe %K European Continental Ancestry Group %K Female %K Fibrin Fibrinogen Degradation Products %K Fibrinogen %K Fibrinolysis %K Genotype %K Humans %K Male %K Middle Aged %K Plasminogen Activator Inhibitor 1 %K Polymorphism, Single Nucleotide %K Prospective Studies %K United States %K Urokinase-Type Plasminogen Activator %X

BACKGROUND AND OBJECTIVES: D-dimer is a hemostasis marker that reflects ongoing fibrin formation and degradation. There is significant inter-individual and inter-population variability in D-dimer concentration, but whether genetic factors underlie these differences is largely unknown. We hypothesized that common coagulation gene variants contribute to differences in circulating D-dimer concentration.

METHODS: The setting was European-American (EA; n = 1858) and African-American (AA; n = 327) unrelated older adults from the Cardiovascular Health Study (CHS), in which we genotyped SNPs in 42 genes related to blood coagulation and fibrinolysis.

RESULTS: Several fibrinogen gene polymorphisms, including the Thr312Ala Aalpha chain variant and the FGG-10034 C/T variant, were associated with approximately 20% higher plasma D-dimer levels in EA (false discovery rate < 5% for covariate-adjusted model). There was also some evidence that a Pro41Leu variant of the PLAU gene encoding urinary plasminogen activator and non-coding polymorphism of the plasminogen activator inhibitor type 1 gene (SERPINE1) were associated with higher plasma D-dimer in EA. There were no significant associations between the studied coagulation or fibrinolysis gene SNPs and plasma D-dimer levels in the smaller AA sample. However, each standard deviation increase in European ancestry assessed by ancestry-informative gene markers was associated with approximately 10% lower mean D-dimer levels in AA.

CONCLUSIONS: Together, common coagulation/fibrinolysis gene SNPs explained only approximately 2% of the variance in plasma D-dimer levels in EA. These findings suggest that the association of D-dimer with risk of vascular outcomes may be mediated largely by environmental factors, other genes, and/or genetic interactions.

%B J Thromb Haemost %V 6 %P 654-9 %8 2008 Apr %G eng %N 4 %1 https://www.ncbi.nlm.nih.gov/pubmed/18208536?dopt=Abstract %R 10.1111/j.1538-7836.2008.02906.x