{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The fibrinogen beta gene (FGB) encodes the Bβ‐chain of fibrinogen, a key plasma glycoprotein that is essential for normal hemostasis, wound healing, and thrombosis. FGB expression in hepatocytes, together with the genes encoding the Aα and γ chains, is tightly regulated by proximal promoters and distal enhancer elements that respond to inflammatory stimuli, thereby determining the quantity of fibrinogen secreted into circulation (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Genetic variation in FGB has been implicated in modulating plasma fibrinogen levels and, in turn, the risk for various cardiovascular and thrombotic disorders. For instance, promoter polymorphisms such as the −455G/A variant have been associated with modest increases in fibrinogen concentration and with altered risk of ischemic stroke and myocardial infarction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition, several genome‐wide association studies have identified common FGB single nucleotide polymorphisms that explain a small, yet significant, portion of the variability in circulating fibrinogen levels."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, rare mutations in FGB, including nonsense, frameshift, and deep intronic variants that alter splicing, can disrupt the synthesis, proper folding, assembly, or secretion of the Bβ‐chain. Such mutations result in conditions ranging from hypofibrinogenemia to congenital afibrinogenemia, with clinical consequences such as bleeding diatheses or, paradoxically, thromboembolic events due to compensatory changes in fibrin clot structure."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": " In some studies, FGB variants have also been shown to interact with inflammatory mediators like interleukin‑6, suggesting that gene–environment interactions may further influence both fibrinogen levels and the risk of cardiovascular disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its well‐defined role in coagulation and thrombosis, aberrant expression of fibrinogen genes, including FGB, has been observed in the context of malignant transformation and metastasis, where altered fibrinogen production may contribute to tumor‐associated thrombosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Collectively, these studies underscore the multifaceted role of FGB in determining fibrinogen quantity and function, with both common regulatory variants and rare deleterious mutations exerting significant biological and clinical effects."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "16"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Richard J Fish, Marguerite Neerman-Arbez "}, {"type": "b", "children": [{"type": "t", "text": "Fibrinogen gene regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1160/TH12-04-0273"}], "href": "https://doi.org/10.1160/TH12-04-0273"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22836683"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22836683"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Maria Sabater-Lleal, Jie Huang, Daniel Chasman, et al. 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