{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T11:50:52Z","timestamp":1773229852523,"version":"3.50.1"},"reference-count":100,"publisher":"Georg Thieme Verlag KG","issue":"02","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Thromb Hemost"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tissue factor (TF) is the primary initiator of blood coagulation in humans. As improper intravascular TF expression and procoagulant activity underlie numerous thrombotic disorders, there has been longstanding interest in the contribution of heritable genetic variation in F3, the gene encoding TF, to human disease. This review seeks to comprehensively and critically synthesize small case\u2013control studies focused on candidate single nucleotide polymorphisms (SNPs), as well as modern genome-wide association studies (GWAS) seeking to discover novel associations between variants and clinical phenotypes. Where possible, correlative laboratory studies, expression quantitative trait loci, and protein quantitative trait loci are evaluated to glean potential mechanistic insights. Most disease associations implicated in historical case\u2013control studies have proven difficult to replicate in large GWAS. Nevertheless, SNPs linked to F3, such as rs2022030, are associated with increased F3 mRNA expression, monocyte TF expression after endotoxin exposure, and circulating levels of the prothrombotic biomarker D-dimer, consistent with the central role of TF in the initiation of blood coagulation.<\/jats:p>","DOI":"10.1055\/s-0043-1769079","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T22:37:06Z","timestamp":1684449426000},"page":"188-199","source":"Crossref","is-referenced-by-count":5,"title":["Human Genetic Variation in F3 and Its Impact on Tissue Factor\u2013Dependent Disease"],"prefix":"10.1055","volume":"50","author":[{"given":"Jin K.","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Health, Sciences, and Technology, Massachusetts Institute of Technology and Harvard Medical School, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marisa A.","family":"Brake","sequence":"additional","affiliation":[{"name":"Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sol","family":"Schulman","sequence":"additional","affiliation":[{"name":"Division of Health, Sciences, and Technology, Massachusetts Institute of Technology and Harvard Medical School, Boston, Massachusetts"},{"name":"Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts"},{"name":"Division of Hematology and Hematologic Malignancies, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2023,5,18]]},"reference":[{"issue":"01","key":"ref1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0092-8674(87)90669-6","article-title":"Molecular cloning of the cDNA for tissue factor, the cellular receptor for the initiation of the coagulation protease cascade","volume":"50","author":"J H Morrissey","year":"1987","journal-title":"Cell"},{"issue":"01","key":"ref2","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/0049-3848(87)90349-5","article-title":"Cloning and expression of human tissue factor cDNA","volume":"48","author":"K L Fisher","year":"1987","journal-title":"Thromb Res"},{"issue":"17","key":"ref3","doi-asserted-by":"crossref","first-page":"5234","DOI":"10.1021\/bi00391a004","article-title":"Human tissue factor: cDNA sequence and chromosome localization of the gene","volume":"26","author":"E M Scarpati","year":"1987","journal-title":"Biochemistry"},{"issue":"15","key":"ref4","doi-asserted-by":"crossref","first-page":"5148","DOI":"10.1073\/pnas.84.15.5148","article-title":"Isolation of cDNA clones coding for human tissue factor: primary structure of the protein and cDNA","volume":"84","author":"E K Spicer","year":"1987","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/380041a0","article-title":"The crystal structure of the complex of blood coagulation factor VIIa with soluble tissue factor","volume":"380","author":"D W Banner","year":"1996","journal-title":"Nature"},{"issue":"12","key":"ref6","doi-asserted-by":"crossref","first-page":"5260","DOI":"10.1073\/pnas.74.12.5260","article-title":"Activation of factor IX by the reaction product of tissue factor and factor VII: additional pathway for initiating blood coagulation","volume":"74","author":"B Osterud","year":"1977","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"07","key":"ref7","doi-asserted-by":"crossref","first-page":"4834","DOI":"10.1016\/S0021-9258(18)42907-9","article-title":"The evaluation of complex-dependent alterations in human factor VIIa","volume":"267","author":"J H Lawson","year":"1992","journal-title":"J Biol Chem"},{"issue":"06","key":"ref8","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1055\/s-0038-1649709","article-title":"Importance of substrate composition, pH and other variables on tissue factor enhancement of factor VIIa activity","volume":"70","author":"P F Neuenschwander","year":"1993","journal-title":"Thromb Haemost"},{"issue":"04","key":"ref9","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1016\/S0021-9258(18)52223-7","article-title":"Phospholipid-independent and -dependent interactions required for tissue factor receptor and cofactor function","volume":"266","author":"W Ruf","year":"1991","journal-title":"J Biol Chem"},{"issue":"04","key":"ref10","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/0092-8674(88)90567-3","article-title":"The molecular basis of blood coagulation","volume":"53","author":"B Furie","year":"1988","journal-title":"Cell"},{"issue":"05","key":"ref11","first-page":"1087","article-title":"Selective cellular expression of tissue factor in human tissues. 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