{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T23:14:33Z","timestamp":1792278873804,"version":"4.4.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ATVB"],"published-print":{"date-parts":[[1999,12]]},"abstract":"<jats:p><jats:italic>Abstract<\/jats:italic>\u2014Plasma fibrinogen is a major risk factor for coronary heart disease, stroke, and peripheral artery disease. There is evidence that genetic variation in the \u03b2-fibrinogen gene contributes to the rate of synthesis of fibrinogen, but the molecular mechanism underlying the genetic heritability of the plasma fibrinogen concentration is largely unknown. We evaluated the physiological roles of 5 common nucleotide substitutions in the promoter region of the \u03b2-fibrinogen gene at positions \u2212148, \u2212249, \u2212455, \u2212854, and \u2212993 from the transcriptional start site. Electrophoretic mobility shift assays revealed distinct differences in the binding characteristics of nuclear proteins between wild-type and mutant fragments of both the \u2212455G\/A and \u2212854G\/A polymorphisms, whereas no clear differences were observed for the \u2212148C\/T, \u2212249C\/T, and \u2212993C\/T sites. Transfection studies in HepG2 cells showed increased basal rates of transcription for both the G-to-A substitution at position \u2212455 (+50%,<jats:italic>P<\/jats:italic>&lt;0.05) and the G-to-A substitution at \u2212854 (+51%,<jats:italic>P<\/jats:italic>&lt;0.05). Additional transfection studies using proximal promoter constructs confirmed that both the \u2212455A and \u2212854A alleles independently enhance the basal rate of transcription of the \u03b2-fibrinogen gene. The rare alleles of the nonrelated \u2212455G\/A and \u2212854G\/A polymorphisms were also associated with significantly increased plasma fibrinogen levels in healthy middle-aged men. Overall, the 2 polymorphisms together explained \u224811% of the variation in plasma fibrinogen concentration. It is concluded that the \u2212455G\/A and \u2212854G\/A polymorphisms of the \u03b2-fibrinogen gene are physiologically relevant mutations with a significant impact on the plasma fibrinogen concentration.<\/jats:p>","DOI":"10.1161\/01.atv.19.12.3063","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T19:44:19Z","timestamp":1308339859000},"page":"3063-3070","source":"Crossref","is-referenced-by-count":100,"title":["Two Common, Functional Polymorphisms in the Promoter Region of the \u03b2-Fibrinogen Gene Contribute to Regulation of Plasma Fibrinogen Concentration"],"prefix":"10.1161","volume":"19","author":[{"given":"Ferdinand M.","family":"van \u2019t Hooft","sequence":"first","affiliation":[{"name":"From the Atherosclerosis Research Unit (F.M.v.H., S.J.F.v.B., A.S., P.E., A.H.), King Gustaf V Research Institute, Department of Medicine, Karolinska Hospital, and the Division of Genetic Epidemiology (A.I.), Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara J. F.","family":"von Bahr","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit (F.M.v.H., S.J.F.v.B., A.S., P.E., A.H.), King Gustaf V Research Institute, Department of Medicine, Karolinska Hospital, and the Division of Genetic Epidemiology (A.I.), Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Silveira","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit (F.M.v.H., S.J.F.v.B., A.S., P.E., A.H.), King Gustaf V Research Institute, Department of Medicine, Karolinska Hospital, and the Division of Genetic Epidemiology (A.I.), Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Iliadou","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit (F.M.v.H., S.J.F.v.B., A.S., P.E., A.H.), King Gustaf V Research Institute, Department of Medicine, Karolinska Hospital, and the Division of Genetic Epidemiology (A.I.), Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Eriksson","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit (F.M.v.H., S.J.F.v.B., A.S., P.E., A.H.), King Gustaf V Research Institute, Department of Medicine, Karolinska Hospital, and the Division of Genetic Epidemiology (A.I.), Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Hamsten","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit (F.M.v.H., S.J.F.v.B., A.S., P.E., A.H.), King Gustaf V Research Institute, Department of Medicine, Karolinska Hospital, and the Division of Genetic Epidemiology (A.I.), Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(57)90768-7"},{"key":"e_1_3_2_2_2","first-page":"270","volume":"2","year":"1957","journal-title":"Lancet"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198408233110804"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(86)90111-X"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1987.03400090067035"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.83.3.836"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/atv91.14.1.8274478"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-118-12-199306150-00008"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.303.6803.605"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)90596-U"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1657877"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)92556-6"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119499"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)92557-8"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1642456"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","unstructured":"Livshits G Blettner M Graff E Hoting I Schettler G Brunner D. 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