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The association of alpha-fibrinogen Thr312Ala polymorphism and venous thromboembolism in the LITE study.
Tuesday,2012-11-06 12:08 America/Los_Angeles — eenright
| Title | The association of alpha-fibrinogen Thr312Ala polymorphism and venous thromboembolism in the LITE study. |
| Publication Type | Journal Article |
| Year of Publication | 2007 |
| Authors | Rasmussen-Torvik, LJ, Cushman, M, Tsai, MY, Zhang, Y, Heckbert, SR, Rosamond, WD, Folsom, AR |
| Journal | Thromb Res |
| Volume | 121 |
| Issue | 1 |
| Pagination | 1-7 |
| Date Published | 2007 |
| ISSN | 0049-3848 |
| Keywords | African Continental Ancestry Group, Aged, Case-Control Studies, European Continental Ancestry Group, Female, Fibrinogen, Genotype, Humans, Logistic Models, Male, Middle Aged, Mutation, Missense, Polymorphism, Genetic, Venous Thromboembolism |
| Abstract | <p><b>INTRODUCTION: </b>The alpha-fibrinogen Thr312Ala variant has been shown to influence clot structure through increased factor XIII cross-linking and formation of thicker fibrin fibers. However, the effect of this common variant on risk of venous thromboembolism (VTE) is unclear. This paper reports the association between the Thr312Ala variant and VTE in the LITE study.</p><p><b>MATERIALS AND METHODS: </b>506 cases and 1014 controls frequency matched on age, sex, race, and study were drawn from two prospective studies and included in the analysis. Logistic regression was used to examine the association between Thr312Ala and VTE.</p><p><b>RESULTS: </b>In a logistic regression model minimally adjusted for the matching variables, the Thr312Ala TA and AA genotypes were associated with a significantly higher risk of VTE than the TT genotype (TA OR and 95% confidence interval 1.27 [1.01-1.60], AA OR 1.49 [1.00-2.22]). Associations were similar in analyses of PE and DVT considered separately and across racial and study subgroups. The association between alpha-fibrinogen Thr312Ala and VTE was modified by both BMI and the FXIII Val34Leu variant; the combination of elevated BMI or FXIII Val34Leu with alpha-fibrinogen Thr312Ala conveyed lower odds of VTE than would be expected by an additive or multiplicative model of individual risk factors.</p><p><b>CONCLUSIONS: </b>These results suggest that alpha-fibrinogen Thr312Ala is involved in the pathogenesis of VTE and that its action may be modified by other VTE risk factors.</p> |
| DOI | 10.1016/j.thromres.2007.02.008 |
| Alternate Journal | Thromb Res |
| PubMed ID | 17433418 |
| PubMed Central ID | PMC2679171 |
| Grant List | N01HC55020 / HL / NHLBI NIH HHS / United States N01HC55018 / HL / NHLBI NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States N01-HC75150 / HC / NHLBI NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States R01 HL59367 / HL / NHLBI NIH HHS / United States N01HC55022 / HL / NHLBI NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC55015 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States R01 HL059367-08 / HL / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States N01HC55016 / HL / NHLBI NIH HHS / United States N01HC55019 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States N01HC55021 / HL / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States T32 HL07972 / HL / NHLBI NIH HHS / United States T32 HL007972 / HL / NHLBI NIH HHS / United States |