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Common hemostasis and inflammation gene variants and venous thrombosis in older adults from the Cardiovascular Health Study.
Tuesday,2012-11-06 12:18 America/Los_Angeles — eenright
| Title | Common hemostasis and inflammation gene variants and venous thrombosis in older adults from the Cardiovascular Health Study. |
| Publication Type | Journal Article |
| Year of Publication | 2009 |
| Authors | Reiner, AP, Lange, LA, Smith, NL, Zakai, NA, Cushman, M, Folsom, AR |
| Journal | J Thromb Haemost |
| Volume | 7 |
| Issue | 9 |
| Pagination | 1499-505 |
| Date Published | 2009 Sep |
| ISSN | 1538-7836 |
| Keywords | Aged, Alleles, Factor V, Factor VIII, Female, Hemostasis, Humans, Inflammation, Male, Middle Aged, Models, Genetic, Plasminogen, Prothrombin, Risk, Serine Endopeptidases, Venous Thrombosis |
| Abstract | <p><b>BACKGROUND/OBJECTIVES: </b>Age-related changes in blood coagulation and fibrinolysis are associated with increased risk of thrombotic events. Inherited deficiencies of coagulation proteins, such as factor V (FV) Leiden and prothrombin G20210A, explain a small fraction of venous thromboembolic disease (VTE). Additional genetic factors are likely to underlie the etiology of VTE, some of which may become manifest at older ages.</p><p><b>METHODS: </b>We tested 290 common SNPs within 51 thrombosis and inflammation genes for association with VTE in the Cardiovascular Health Study, a large, prospective cohort of older adults followed for up to 12 years.</p><p><b>RESULTS: </b>There were 184 VTE events that occurred at mean age of 78 years. TagSNPs within four genes encoding FXIII subunit A (F13A), FVII activating protease (HABP2), protease activated receptor-1 (F2R) and the urokinase receptor (PLAUR) showed the strongest evidence for association with VTE, with each gene having a global P-value < 0.05 and at least one tagSNP false discovery rate (FDR) q-value < 0.05. The rs3024409 variant allele of F13A1 was associated with 1.66-fold increased risk of VTE, while the minor alleles of HABP2 rs6585234 and rs3862019, F2R rs253061 and rs153311, and PLAUR rs344782 were each associated with lower risk of VTE (hazard ratios in the range of 0.49-0.66). Consistent with the observed protective association for VTE risk, the HABP2 rs3862019 variant allele was also associated with lower activity levels of coagulation factors FVIII, FIX, FX and plasminogen. We also confirm previously reported associations between common variants of the coagulation FII, FV, FVIII, FXI, alpha-fibrinogen and protein C genes and risk of VTE.</p><p><b>CONCLUSIONS: </b>These findings suggest that several novel common coagulation gene variants may be related to risk of VTE in older adults. Further studies in older adults are needed to validate these findings and assess functional molecular mechanisms.</p> |
| DOI | 10.1111/j.1538-7836.2009.03522.x |
| Alternate Journal | J. Thromb. Haemost. |
| PubMed ID | 19552680 |
| PubMed Central ID | PMC2853009 |
| Grant List | R01 HL071862-05A1 / HL / NHLBI NIH HHS / United States P30 AG024827 / AG / NIA NIH HHS / United States R01 AG-15928 / AG / NIA NIH HHS / United States R01 HL075366 / HL / NHLBI NIH HHS / United States R01 AG015928 / AG / NIA NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States R01 HL-075366 / HL / NHLBI NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States R01 HL59367 / HL / NHLBI NIH HHS / United States P30-AG-024827 / AG / NIA NIH HHS / United States R01 HL-071862 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States AG-027058 / AG / NIA NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States R01 HL071862 / HL / NHLBI NIH HHS / United States R01 AG-20098 / AG / NIA NIH HHS / United States R01 AG020098 / AG / NIA NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States U01HL080295 / HL / NHLBI NIH HHS / United States AG-023629 / AG / NIA NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States R01 AG027058 / AG / NIA NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States R56 AG023629 / AG / NIA NIH HHS / United States |