rs1799963
badMag 7.0This is a 3 prime utr variant variant in the F2 gene.
Key Literature Trait Associations
Venous Thromboembolism
The Prothrombin G20210A variant sits in the 3' untranslated region of the prothrombin gene and enhances RNA processing, leading to ~30% higher circulating prothrombin (Factor II) levels. Elevated prothrombin tips the coagulation balance toward clot formation, giving heterozygous carriers roughly a 2-4-fold higher risk of deep-vein thrombosis or pulmonary embolism. It is the second most common inherited thrombophilia in European populations, found in about 1-3% of that group.
Venous thromboembolism in pregnancy
Pregnancy amplifies the thrombotic risk conferred by the prothrombin 20210A allele due to the natural procoagulant shift of gestation. A 2015 meta-analysis of 12 case-control studies found OR=5.43 (95% CI 3.66–8.03) for VTE during pregnancy among PT G20210A carriers. A 2017 Bayesian meta-analysis of 36 studies estimated absolute antepartum/postpartum risk below 3% for heterozygotes, indicating that while relative risk is substantial, absolute risk remains moderate. Guidelines from ACOG and RCOG recommend thromboprophylaxis assessment for pregnant carriers.
Ischemic stroke
The prothrombin 20210A allele is associated with increased arterial ischemic stroke risk, particularly in children and young adults. A 2017 meta-analysis of 30 case-control studies found OR=1.83 in children and OR=1.69 in young adults. The mechanism involves elevated prothrombin promoting thrombus formation in cerebral vessels. ClinVar lists ischemic stroke as a Risk Factor condition for this variant. The association appears strongest below age 55 and in European populations; data in other ancestries are sparse.
Myocardial infarction
The prothrombin G20210A variant modestly increases myocardial infarction risk, with effects most pronounced in younger individuals. A 2017 systematic review and meta-analysis of 34 studies (14,611 MI cases, 84,358 controls) found an overall OR of 1.43 (95% CI 1.18–1.72) in the allele model, rising to OR=1.76 (95% CI 1.32–2.35) in those under 55 years. The association is significant in Caucasian populations but not robustly demonstrated in non-Caucasians. The effect is considered secondary to the variant's primary prothrombotic mechanism.
Preeclampsia
The prothrombin 20210A allele is associated with approximately doubled risk of severe preeclampsia. A 2014 HuGE review of 57 studies (5,049 cases, 16,989 controls) reported OR=2.01 (95% CI 1.14–3.55) with minimal heterogeneity (I²=0%). A broader 2012 field synopsis of genetic associations confirmed OR=1.72 (99% CI 1.31–2.26) for preeclampsia, designated as having moderate epidemiological credibility. The mechanism likely involves placental hypoperfusion from microthrombosis in uteroplacental vessels.
▶GWAS Catalog Trait Associations (15)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
GWAS Catalog Trait Associations (15)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
▶ClinVar annotation
Ischemic stroke; Pregnancy loss, recurrent, susceptibility to, 2; Congenital prothrombin deficiency; Venous thromboembolism; not provided; Cerebral palsy; Thrombophilia caused by F2 prothrombin deficiency; Congenital prothrombin deficiency;Pregnancy loss, recurrent, susceptibility to, 2;Thrombophilia due to thrombin defect;Ischemic stroke; Thrombophilia due to thrombin defect; Inborn genetic diseases
View on ClinVar →▶Research that mentions this SNP (7)
▶Myocardial infarction, prothrombotic genotypes, and venous thrombosis risk: The Tromsø StudyAssociationN=2,402Joakim K. Sejrup et al.(2020)· Research and Practice in Thrombosis and Haemostasis
Prospective case-cohort study examining whether 5 prothrombotic SNPs explain the increased venous thromboembolism (VTE) risk after myocardial infarction (MI). Patients with MI had a 1.4-fold increased VTE risk (HR 1.44, 95% CI 1.07-1.96), but adjustment for rs8176719 (ABO), rs6025 (F5), rs1799963 (F2), rs2066865 (FGG), and rs2036914 (F11) did not attenuate this relationship (adjusted HR 1.52). Individual SNPs associated with VTE in non-MI subjects (F5 HR 2.20, ABO HR 1.44), but their combination with MI did not yield excess VTE risk.
▶Genetic variants conferring susceptibility to gastroschisis: a phenomenon restricted to the interaction with the environment?Meta-analysisN=434Victor M. Salinas-Torres et al.(2018)· Pediatric Surgery International
This systematic review analyzed genetic associations with gastroschisis from 1980-2017, identifying 14 SNPs from 10 genes associated with crude risk and 30 SNPs from 14 genes with stratified risk. Four SNPs showed significant associations: rs4961 (ADD1, p=0.023), rs5443 (GNB3, p=0.002), rs1042713 (ADRB2, p=0.007), and rs1042714 (ADRB2, p=0.006). The findings suggest genetic susceptibility in gastroschisis is not restricted to gene-environment interactions, with blood pressure regulation genes playing a significant role in vascular disruption pathogenesis.
▶Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization studyMeta-analysisN=60,139Sara Lindström et al.(2017)· Human Genetics
Mendelian Randomization study examining the causal relationship between obesity (BMI) and venous thromboembolism using 95 BMI-associated SNPs in 7,507 VTE cases and 52,632 European ancestry controls. FTO rs1558902 showed the strongest individual association with VTE (OR 1.07, P = 0.005), and genetically predicted high BMI was significantly associated with increased VTE risk (OR 1.59 per SD increase in BMI, P = 5.8 × 10^-6), providing evidence for a causal relationship between obesity and VTE.
▶Vascular endothelial growth factor (VEGF) gene polymorphisms may influence the efficacy of thalidomide in multiple myelomaAssociationN=237Niels F. Andersen et al.(2012)· International Journal of Cancer
This case-control association study examined genetic polymorphisms in 237 Russian women to identify variants associated with early reproductive loss and recurrent miscarriage. The study found that DNMT3B rs2424913 (OR=4.44-4.78), DNMT1 rs2228611 (OR=3.0-3.94), and DNMT1 rs8101626 (OR=2.5-3.1) were significantly associated with increased risk of sporadic and recurrent early pregnancy loss, while SYCP3 rs769825641 heterozygotes showed elevated risk of sporadic miscarriage.
▶Evaluation of genes involved in limb development, angiogenesis, and coagulation as risk factors for congenital limb deficienciesAssociationN=1,369Marilyn L. Browne et al.(2012)· American Journal of Medical Genetics Part A
Population-based case-control study of 389 infants with congenital limb deficiencies and 980 controls examining 132 SNPs in 20 candidate genes involved in limb development, angiogenesis, and coagulation. Among non-Hispanic white infants, SNPs in FGF10 (rs10805683: OR=1.99, 95% CI=1.43-2.77; rs13170645: OR=2.37, 95% CI=1.48-3.78) showed significant associations with limb deficiencies after multiple testing correction, with supportive evidence for genes including EN1, WNT7A, CYP26B1, SHH, and TBX5.
▶Genetic Predictors of Response to Photodynamic TherapyReviewFrancesco Parmeggiani et al.(2011)· Molecular Diagnosis & Therapy
Comprehensive review evaluating SNPs as genetic predictors of choroidal neovascularization (CNV) response to photodynamic therapy with verteporfin (PDT-V). The paper examines pharmacogenetic correlations for thrombo-coagulative pathway variants (MTHFR rs1801133, F5 rs6025, F2 rs1799963, F13A1 rs5985), complement/inflammatory variants (CFH, HTRA1, CRP, ARMS2), and VEGFA variants (rs699947, rs2146323), concluding that specific SNPs show clinical plausibility as markers to optimize PDT-V efficacy and guide therapeutic approaches in neovascular macular degeneration.
▶Risk variants for atrial fibrillation on chromosome 4q25 associate with ischemic strokeReviewGretarsdottir S. et al.(2008)· Annals of Neurology
This review examines 15 years of ischemic stroke susceptibility gene research, organized into three periods: early candidate gene studies (1985-1995) testing variants in hemostasis and homocysteine metabolism genes; expansion period with functional variants discovered from other diseases tested on larger stroke cohorts; and current GWAS-driven large-scale genotyping studies. Key findings include identification of susceptibility loci in CELSR1 (rs6007897, rs4044210 in Japanese populations), PITX2 (rs2200733, rs10033464), and other genes involved in lipid metabolism (APOA5, APOCIII, MLXIPL) and signal transduction (PDE4D, ALOX5AP), with evidence that alleles are often shared across diseases and that careful clinical stratification is critical.
Gene information from NCBI Gene. Variant classifications from ClinVar.
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