|(A;A)||7||6.74x risk of thrombosis; 2-20x risk for cerebral stroke if PFO+|
|(A;G)||2.8||2.8x risk of thrombosis; higher risk for cerebral stroke if PFO+|
|(G;G)||0||normal/common risk of thrombosis|
Due to the interactions of the corresponding protein with the Factor V protein, SNPs in these two coagulation-related genes are often studied together. In particular, rs1799963 is often studied together with rs6025.
[PMID 23900608]In a 2013 meta-analysis of 31 databases, the analysis of i3002432 / rs1799963 (PT20210A or prothrombin or Factor 2) was based on 9,134 cases and 17,606 controls. The AG variant average risk for Venous Thromboembolism was 2.8, and risk was higher for younger subjects ((< 45 years old, OR: 3.19; ≥ 45 years old, OR: 2.57) and for women taking oral contraceptives (women not using OCs, OR: 2.73; women using OCs, OR: 5.58). Further analysis by outcome revealed that more the risk for Cerebral venous sinus thrombosis was highest at 4.4 (based on 303 cases and 2,723 controls), whereas for Venous thromboembolism OR was 3.0, and for Venous thrombosis (w/o pulmonary embolism) OR 2.6. The AA variant risk was 6.74, but the odds ratio for homozygotes was based on only 28 subjects among cases and 4 controls. A larger risk was seen in rs6025 Factor V Leiden SNP variants.
For a more complete discussion, see rs6025.
[PMID 19404532],[PMID 22784820] In addition to the literature associating the G20210A variant with thromboembolism in general, several studies have found that this variant significantly (2 - 20 fold) increases the risk for ischemic stroke (aka cerebral ischemia) in individuals with patent foramen ovale (PFO), or hole in the heart. It is estimated that PFO is present in ~25% of the (normal/healthy) population.
[PMID 19786296] Platelet glycoprotein GP VI 13254C allele is an independent risk factor of premature myocardial infarction
[PMID 21291465] The association of genetic polymorphisms with cerebral palsy: a meta-analysis
[PMID 21332313] Sequence variations in the FII, FV, F13A1, FGB and PAI-1 genes are associated with differences in myocardial perfusion
[PMID 22147897] Comparative incidence of a first thrombotic event in purely obstetric antiphospholipid syndrome with pregnancy loss: the NOH-APS observational study
[PMID 22198364] The association of inherited thrombophilia and intrauterine fetal death: a case-control study
[PMID 21913742] Genetic predictors of response to photodynamictherapy
[PMID 22421107] The G534E-polymorphism of the gene encoding the Factor VII-activating protease is a risk factor for venous thrombosis and recurrent events
[PMID 22675575] Caution in Interpreting Results from Imputation Analysis When Linkage Disequilibrium Extends over a Large Distance: A Case Study on Venous Thrombosis
[PMID 16846490] Lemierre's syndrome and genetic polymorphisms: a case report.
[PMID 17107626] Comparison of PrASE and Pyrosequencing for SNP Genotyping.
[PMID 18513389] New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background.
[PMID 18752569] Factor V Leiden is associated with pre-eclampsia but not with fetal growth restriction: a genetic association study and meta-analysis.
[PMID 18936436] Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991-1994.
[PMID 19131662] A meta-analysis of candidate gene polymorphisms and ischemic stroke in 6 study populations: association of lymphotoxin-alpha in nonhypertensive patients.
[PMID 19330901] Association of 77 polymorphisms in 52 candidate genes with blood pressure progression and incident hypertension: the Women's Genome Health Study.
[PMID 19538716] Thrombotic genetic risk factors and warfarin pharmacogenetic variants in Sao Miguel's healthy population (Azores).
[PMID 19559392] A candidate gene association study of 77 polymorphisms in migraine.
[PMID 19591822] Prevalence of genetic thrombophilic polymorphisms in the Sri Lankan population--implications for association study design and clinical genetic testing services.
[PMID 20031567] An evaluation of candidate genes of inflammation and thrombosis in relation to the risk of venous thromboembolism: The Women's Genome Health Study.
[PMID 20078877] Gene polymorphisms in association with emerging cardiovascular risk markers in adult women.
[PMID 20352152] Association of common genetic variations and idiopathic venous thromboembolism. Results from EDITh, a hospital-based case-control study.
[PMID 21239755] Functional polymorphisms of the coagulation factor II gene (F2) and susceptibility to systemic lupus erythematosus.
[PMID 21422408] Clotting factor gene polymorphisms and colorectal cancer risk.
[PMID 22388798] Gene panels to help identify subgroups at high and low risk of coronary heart disease among those randomized to antihypertensive treatment: the GenHAT study.
[PMID 23132613] Genetic association studies in pre-eclampsia: systematic meta-analyses and field synopsis
[PMID 24226152] Influence of single nucleotide polymorphisms on thrombin generation in factor V Leiden heterozygotes
[PMID 23533563] Novel risk factors for premature peripheral arterial occlusive disease in non-diabetic patients: a case-control study.
[PMID 25028703] Maternal Genotype and Severe Preeclampsia: A HuGE Review
[PMID 25210051] Genetic Variations Associated with Recurrent Venous Thrombosis
|Disease||Thrombophilia Ischemic stroke Pregnancy loss Prothrombin deficiency|
|CLNDBN||Thrombophilia Ischemic stroke, susceptibility to Pregnancy loss, recurrent, susceptibility to, 2 Prothrombin deficiency, congenital|
|CLNSRC||OMIM Allelic Variant|
|CLNACC||RCV000014237.19, RCV000014238.3, RCV000022729.3, RCV000205022.2,|
[PMID 25992517] Lack of association between the prothrombin rs1799963 polymorphism and juvenile myoclonic epilepsy
[PMID 29094466] Joint effects of prothrombotic genotypes and body height on the risk of venous thromboembolism: The Tromsø Study.
[PMID 30773804] Effect of prothrombotic genotypes on the risk of venous thromboembolism in patients with and without ischemic stroke.The TromsØ Study.
[PMID 32110755] Myocardial infarction, prothrombotic genotypes, and venous thrombosis risk: The Tromsø Study.