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Common genetic variants associated with plasma fibrin D-dimer concentration in older European- and African-American adults.
Tuesday,2012-11-06 12:09 America/Los_Angeles — eenright
| Title | Common genetic variants associated with plasma fibrin D-dimer concentration in older European- and African-American adults. |
| Publication Type | Journal Article |
| Year of Publication | 2008 |
| Authors | Lange, LA, Reiner, AP, Carty, CL, Jenny, NS, Cushman, M, Lange, EM |
| Journal | J Thromb Haemost |
| Volume | 6 |
| Issue | 4 |
| Pagination | 654-9 |
| Date Published | 2008 Apr |
| ISSN | 1538-7836 |
| Keywords | Africa, African Americans, Aged, Aged, 80 and over, Blood Coagulation, Europe, European Continental Ancestry Group, Female, Fibrin Fibrinogen Degradation Products, Fibrinogen, Fibrinolysis, Genotype, Humans, Male, Middle Aged, Plasminogen Activator Inhibitor 1, Polymorphism, Single Nucleotide, Prospective Studies, United States, Urokinase-Type Plasminogen Activator |
| Abstract | <p><b>BACKGROUND AND OBJECTIVES: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p> |
| DOI | 10.1111/j.1538-7836.2008.02906.x |
| Alternate Journal | J Thromb Haemost |
| PubMed ID | 18208536 |
| PubMed Central ID | PMC: N/A |
| Grant List | N01 HC-15103 / HC / NHLBI NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States R01 HL-071862 / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States |