The Heterozygous 20210 G/A Prothrombin Genotype Is Associated With Early Venous Thrombosis in Inherited Thrombophilias and Is Not Increased in Frequency in Artery Disease
A genetic variation in the 3'-untranslated region of the prothrombin mRNA (20210 G/A) has recently been reported to be associated with elevated plasma prothrombin levels and with an increased incidence of venous thrombosis. We determined the frequency of this mutation, the detection of which wa...
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| Published in | Arteriosclerosis, thrombosis, and vascular biology Vol. 17; no. 11; pp. 2418 - 2422 |
|---|---|
| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Philadelphia, PA
American Heart Association, Inc
01.11.1997
Hagerstown, MD Lippincott |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1079-5642 1524-4636 |
| DOI | 10.1161/01.ATV.17.11.2418 |
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| Abstract | A genetic variation in the 3'-untranslated region of the prothrombin mRNA (20210 G/A) has recently been reported to be associated with elevated plasma prothrombin levels and with an increased incidence of venous thrombosis. We determined the frequency of this mutation, the detection of which was improved by allele-specific amplification of exon 14 and by denaturing gradients (denaturing gradient gel electrophoresis), in cohorts of patients affected by venous thrombosis (n = 132) or by coronary or cerebrovascular diseases (n = 195) and in normal subjects from various populations. An overlapping frequency of the heterozygous genotype (4%) was found in normal subjects from Italy and Cyprus, and no carrier was detected in 40 subjects of Indian or Somali origin. The 20210 GA heterozygous genotype was not increased in frequency in patients with arterial disease. In contrast, the GA genotype was associated (P = .007) with venous thrombosis both in simple heterozygotes (16%) with a family history of thrombosis as well as in double heterozygotes (14%) for other known thrombophilic defects. A synergic interaction between the prothrombin 20210 GA genotype and the factor V Leiden mutation, both potentially affecting the prothrombinase complex, was suggested by the early onset of thrombosis (median age 22 years) in doubly heterozygous patients. The association of the 20210 A allele with higher prothrombin levels was confirmed in the Italian population. However, the prothrombin assay does not allow an efficient preselection of patients for the DNA analysis. (Arterioscler Thromb Vasc Biol. 1997;17:2418-2422.) |
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| AbstractList | A genetic variation in the 3'-untranslated region of the prothrombin mRNA (20210 G/A) has recently been reported to be associated with elevated plasma prothrombin levels and with an increased incidence of venous thrombosis. We determined the frequency of this mutation, the detection of which was improved by allele-specific amplification of exon 14 and by denaturing gradients (denaturing gradient gel electrophoresis), in cohorts of patients affected by venous thrombosis (n = 132) or by coronary or cerebrovascular diseases (n = 195) and in normal subjects from various populations. An overlapping frequency of the heterozygous genotype (4%) was found in normal subjects from Italy and Cyprus, and no carrier was detected in 40 subjects of Indian or Somali origin. The 20210 GA heterozygous genotype was not increased in frequency in patients with arterial disease. In contrast, the GA genotype was associated (P = .007) with venous thrombosis both in simple heterozygotes (16%) with a family history of thrombosis as well as in double heterozygotes (14%) for other known thrombophilic defects. A synergic interaction between the prothrombin 20210 GA genotype and the factor V Leiden mutation, both potentially affecting the prothrombinase complex, was suggested by the early onset of thrombosis (median age 22 years) in doubly heterozygous patients. The association of the 20210 A allele with higher prothrombin levels was confirmed in the Italian population. However, the prothrombin assay does not allow an efficient preselection of patients for the DNA analysis.A genetic variation in the 3'-untranslated region of the prothrombin mRNA (20210 G/A) has recently been reported to be associated with elevated plasma prothrombin levels and with an increased incidence of venous thrombosis. We determined the frequency of this mutation, the detection of which was improved by allele-specific amplification of exon 14 and by denaturing gradients (denaturing gradient gel electrophoresis), in cohorts of patients affected by venous thrombosis (n = 132) or by coronary or cerebrovascular diseases (n = 195) and in normal subjects from various populations. An overlapping frequency of the heterozygous genotype (4%) was found in normal subjects from Italy and Cyprus, and no carrier was detected in 40 subjects of Indian or Somali origin. The 20210 GA heterozygous genotype was not increased in frequency in patients with arterial disease. In contrast, the GA genotype was associated (P = .007) with venous thrombosis both in simple heterozygotes (16%) with a family history of thrombosis as well as in double heterozygotes (14%) for other known thrombophilic defects. A synergic interaction between the prothrombin 20210 GA genotype and the factor V Leiden mutation, both potentially affecting the prothrombinase complex, was suggested by the early onset of thrombosis (median age 22 years) in doubly heterozygous patients. The association of the 20210 A allele with higher prothrombin levels was confirmed in the Italian population. However, the prothrombin assay does not allow an efficient preselection of patients for the DNA analysis. Abstract A genetic variation in the 3′-untranslated region of the prothrombin mRNA (20210 G/A) has recently been reported to be associated with elevated plasma prothrombin levels and with an increased incidence of venous thrombosis. We determined the frequency of this mutation, the detection of which was improved by allele-specific amplification of exon 14 and by denaturing gradients (denaturing gradient gel electrophoresis), in cohorts of patients affected by venous thrombosis (n=132) or by coronary or cerebrovascular diseases (n=195) and in normal subjects from various populations. An overlapping frequency of the heterozygous genotype (4%) was found in normal subjects from Italy and Cyprus, and no carrier was detected in 40 subjects of Indian or Somali origin. The 20210 GA heterozygous genotype was not increased in frequency in patients with arterial disease. In contrast, the GA genotype was associated ( P =.007) with venous thrombosis both in simple heterozygotes (16%) with a family history of thrombosis as well as in double heterozygotes (14%) for other known thrombophilic defects. A synergic interaction between the prothrombin 20210 GA genotype and the factor V Leiden mutation, both potentially affecting the prothrombinase complex, was suggested by the early onset of thrombosis (median age 22 years) in doubly heterozygous patients. The association of the 20210 A allele with higher prothrombin levels was confirmed in the Italian population. However, the prothrombin assay does not allow an efficient preselection of patients for the DNA analysis. A genetic variation in the 3'-untranslated region of the prothrombin mRNA (20210 G/A) has recently been reported to be associated with elevated plasma prothrombin levels and with an increased incidence of venous thrombosis. We determined the frequency of this mutation, the detection of which was improved by allele-specific amplification of exon 14 and by denaturing gradients (denaturing gradient gel electrophoresis), in cohorts of patients affected by venous thrombosis (n = 132) or by coronary or cerebrovascular diseases (n = 195) and in normal subjects from various populations. An overlapping frequency of the heterozygous genotype (4%) was found in normal subjects from Italy and Cyprus, and no carrier was detected in 40 subjects of Indian or Somali origin. The 20210 GA heterozygous genotype was not increased in frequency in patients with arterial disease. In contrast, the GA genotype was associated (P = .007) with venous thrombosis both in simple heterozygotes (16%) with a family history of thrombosis as well as in double heterozygotes (14%) for other known thrombophilic defects. A synergic interaction between the prothrombin 20210 GA genotype and the factor V Leiden mutation, both potentially affecting the prothrombinase complex, was suggested by the early onset of thrombosis (median age 22 years) in doubly heterozygous patients. The association of the 20210 A allele with higher prothrombin levels was confirmed in the Italian population. However, the prothrombin assay does not allow an efficient preselection of patients for the DNA analysis. (Arterioscler Thromb Vasc Biol. 1997;17:2418-2422.) A genetic variation in the 3'-untranslated region of the prothrombin mRNA (20210 G/A) has recently been reported to be associated with elevated plasma prothrombin levels and with an increased incidence of venous thrombosis. We determined the frequency of this mutation, the detection of which was improved by allele-specific amplification of exon 14 and by denaturing gradients (denaturing gradient gel electrophoresis), in cohorts of patients affected by venous thrombosis (n = 132) or by coronary or cerebrovascular diseases (n = 195) and in normal subjects from various populations. An overlapping frequency of the heterozygous genotype (4%) was found in normal subjects from Italy and Cyprus, and no carrier was detected in 40 subjects of Indian or Somali origin. The 20210 GA heterozygous genotype was not increased in frequency in patients with arterial disease. In contrast, the GA genotype was associated (P = .007) with venous thrombosis both in simple heterozygotes (16%) with a family history of thrombosis as well as in double heterozygotes (14%) for other known thrombophilic defects. A synergic interaction between the prothrombin 20210 GA genotype and the factor V Leiden mutation, both potentially affecting the prothrombinase complex, was suggested by the early onset of thrombosis (median age 22 years) in doubly heterozygous patients. The association of the 20210 A allele with higher prothrombin levels was confirmed in the Italian population. However, the prothrombin assay does not allow an efficient preselection of patients for the DNA analysis. |
| Author | Castoldi, E. Ferraresi, P. Palareti, G. Marchetti, G. Cavallari, E. Ardissino, D. Legnani, C. Bernardi, F. Mascoli, F. |
| AuthorAffiliation | Received June 3, 1997; accepted July 22, 1997. From the Dipartimento di Biochimica e Biologia Molecolare, Universita, Ferrara, Italy (P.F., G.M., E.Cav. E.Cas., F.B.); the Unita di Chirurgia Vascolare, Arcispedale S. Anna, Ferrara, Italy (F.M.); the Dipartimento di Angiologia e Coagulazione, Universita-Ospedale S. Orsola, Bologna, Italy (C.L., G.P.); and the Divisione di Cardiologia IRCCS Policlinico San Matteo, Pavia, Italy (D.A.). Correspondence to Prof Francesco Bernardi, Dipartimento di Biochimica e Biologia Molecolare, Centro Interdipartimentale di Biotecnologie Universita degli Studi di Ferrara, Via L. Borsari 46, 44100 Ferrara, Italy. E-mail ber@dns.unife.it |
| AuthorAffiliation_xml | – name: Received June 3, 1997; accepted July 22, 1997. From the Dipartimento di Biochimica e Biologia Molecolare, Universita, Ferrara, Italy (P.F., G.M., E.Cav. E.Cas., F.B.); the Unita di Chirurgia Vascolare, Arcispedale S. Anna, Ferrara, Italy (F.M.); the Dipartimento di Angiologia e Coagulazione, Universita-Ospedale S. Orsola, Bologna, Italy (C.L., G.P.); and the Divisione di Cardiologia IRCCS Policlinico San Matteo, Pavia, Italy (D.A.). Correspondence to Prof Francesco Bernardi, Dipartimento di Biochimica e Biologia Molecolare, Centro Interdipartimentale di Biotecnologie Universita degli Studi di Ferrara, Via L. Borsari 46, 44100 Ferrara, Italy. E-mail ber@dns.unife.it |
| Author_xml | – sequence: 1 givenname: P. surname: Ferraresi fullname: Ferraresi, P. organization: Received June 3, 1997; accepted July 22, 1997. From the Dipartimento di Biochimica e Biologia Molecolare, Universita, Ferrara, Italy (P.F., G.M., E.Cav. E.Cas., F.B.); the Unita di Chirurgia Vascolare, Arcispedale S. Anna, Ferrara, Italy (F.M.); the Dipartimento di Angiologia e Coagulazione, Universita-Ospedale S. Orsola, Bologna, Italy (C.L., G.P.); and the Divisione di Cardiologia IRCCS Policlinico San Matteo, Pavia, Italy (D.A.). Correspondence to Prof Francesco Bernardi, Dipartimento di Biochimica e Biologia Molecolare, Centro Interdipartimentale di Biotecnologie Universita degli Studi di Ferrara, Via L. Borsari 46, 44100 Ferrara, Italy. E-mail ber@dns.unife.it – sequence: 2 givenname: G. surname: Marchetti fullname: Marchetti, G. – sequence: 3 givenname: C. surname: Legnani fullname: Legnani, C. – sequence: 4 givenname: E. surname: Cavallari fullname: Cavallari, E. – sequence: 5 givenname: E. surname: Castoldi fullname: Castoldi, E. – sequence: 6 givenname: F. surname: Mascoli fullname: Mascoli, F. – sequence: 7 givenname: D. surname: Ardissino fullname: Ardissino, D. – sequence: 8 givenname: G. surname: Palareti fullname: Palareti, G. – sequence: 9 givenname: F. surname: Bernardi fullname: Bernardi, F. |
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| Snippet | A genetic variation in the 3'-untranslated region of the prothrombin mRNA (20210 G/A) has recently been reported to be associated with elevated plasma... Abstract A genetic variation in the 3′-untranslated region of the prothrombin mRNA (20210 G/A) has recently been reported to be associated with elevated plasma... |
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| SubjectTerms | Adolescent Adult Age of Onset Aged Alleles Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Cerebrovascular Disorders - epidemiology Cerebrovascular Disorders - genetics Cohort Studies Comorbidity Coronary Disease - epidemiology Coronary Disease - genetics Cyprus - ethnology Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous DNA Mutational Analysis Ethnic Groups - genetics Factor V - analysis Female Gene Frequency Heterozygote Humans India - ethnology Italy - epidemiology Male Medical sciences Middle Aged Point Mutation Polymerase Chain Reaction Polymorphism, Genetic Prothrombin - genetics Puerperal Disorders - epidemiology Puerperal Disorders - genetics Pulmonary Embolism - epidemiology Pulmonary Embolism - etiology Somalia - ethnology Thrombophilia - epidemiology Thrombophilia - genetics Thrombophlebitis - epidemiology Thrombophlebitis - genetics |
| Title | The Heterozygous 20210 G/A Prothrombin Genotype Is Associated With Early Venous Thrombosis in Inherited Thrombophilias and Is Not Increased in Frequency in Artery Disease |
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