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Genetic variation within the anticoagulant, procoagulant, fibrinolytic and innate immunity pathways as risk factors for venous thromboembolism
| Content Provider | Scilit |
|---|---|
| Author | Heit, J. A. Cunningham, J. M. Petterson, T. M. Armasu, S. M. Rider, D. N. Andrade, M. D. E. |
| Copyright Year | 2011 |
| Description | Journal: Journal of Thrombosis and Haemostasis Summary. Background: Venous thromboembolism (VTE) is highly heritable (estimated heritability $[h^{2}$] = 0.62) and likely to be a result of multigenic action. Objective: To systematically test variation within genes encoding for important components of the anticoagulant, procoagulant, fibrinolytic and innate immunity pathways for an independent association with VTE. Methods: Non-Hispanic adults of European ancestry with objectively-diagnosed VTE, and age- and sex- matched controls, were genotyped for 13 031 single nucleotide polymorphisms (SNPs) within 764 genes. Analyses (n = 12 296 SNPs) were performed with plink using an additive genetic model and adjusted for age, sex, state of residence, and myocardial infarction or stroke. Results: Among 2927 individuals, one or more SNPs within ABO, F2, F5, F11, KLKB1, SELP and SCUBE1 were significantly associated with VTE, including factor (F) V Leiden, prothrombin G20210A, ABO non-O blood type, and a novel association with ABO rs2519093 (OR = 1.68, P-value = 8.08 × $10^{−16}$) that was independent of blood type. In stratified analyses, SNPs in the following genes were significantly associated with VTE: F5 and ABO among both genders and LY86 among women; F2, ABO and KLKB1 among FV Leiden non-carriers; F5, F11, KLKB1 and GFRA1 in those with ABO non-O blood type; and ABO, F5, F11, KLKB1, SCUBE1 and SELP among prothrombin G20210A non-carriers. The ABO rs2519093 population-attributable risk (PAR) exceeded that of FV Leiden and prothrombin G20210A, and the joint PAR of FV Leiden, prothrombin G20210A, ABO non-O and ABO rs2519093 was 0.40. Conclusions: Anticoagulant, procoagulant, fibrinolytic and innate immunity pathway genetic variation accounts for a large proportion of VTE among non-Hispanic adults of European ancestry. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110632/pdf |
| Ending Page | 1142 |
| Page Count | 10 |
| Starting Page | 1133 |
| e-ISSN | 15387836 |
| DOI | 10.1111/j.1538-7836.2011.04272.x |
| Journal | Journal of Thrombosis and Haemostasis |
| Issue Number | 6 |
| Volume Number | 9 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2011-04-04 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Thrombosis and Haemostasis Nutrition and Dietetics Deep Vein Thrombosis Pulmonary Embolism Venous Thromboembolism |
| Content Type | Text |
| Resource Type | Article |
