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Plasma thrombin-activatable fibrinolysis inhibitor antigen concentration and genotype in relation to myocardial infarction in the north and south of Europe.
Arterioscler Thromb Vasc Biol 2002; 22(5):867-73AT

Abstract

The thrombin-activatable fibrinolysis inhibitor (TAFI) is a recently described inhibitor of fibrinolysis that decreases plasminogen binding to the fibrin surface. The plasma TAFI concentration is almost entirely genetically determined. We investigated whether plasma TAFI levels and polymorphisms located in the TAFI gene could constitute risk markers of myocardial infarction (MI). Plasma TAFI antigen (Ag) levels were assayed by ELISA and 2 TAFI gene polymorphisms (Ala147Thr and C+1542G in the 3' untranslated region) were determined in a large European case-control study. This study compared 598 men recruited 3 to 6 months after MI with 653 age-matched controls from North Europe (Stockholm, Sweden, and London, England) and South Europe (Marseilles, France, and San Giovanni Rotondo, Italy). A TAFI Ag value above the 90th percentile was associated with a significantly lower risk of MI (odds ratio 0.55, P<0.02), indicating that elevated TAFI may be protective against MI. As previously shown, the 2 TAFI gene polymorphisms were in strong linkage disequilibrium and were associated with the TAFI Ag concentration, with carriers of the Thr147 and 1542C alleles having higher levels (P<0.0005). These effects were similar in controls and cases and in each center. There was a difference in allele frequency between cases and controls for the Ala147Thr polymorphism, with Thr147 allele carriers being more frequent in controls than in cases in 2 centers, Stockholm (P=0.03) and San Giovanni Rotondo (P=0.03); the odds ratio for the entire cohort was 0.78 (P<0.05). In conclusion, patients with a recent MI presented lower values of TAFI Ag and higher frequencies of the "TAFI-decreasing" alleles. The geographical differences observed do not contribute to explaining the North-South gradient in MI risk in Europe.

Authors+Show Affiliations

Laboratoire d'Hématologie, CHU Timone, Inserm EPI 99-36, Marseilles, France. ijuhan@ap-hm.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12006404

Citation

Juhan-Vague, I, et al. "Plasma Thrombin-activatable Fibrinolysis Inhibitor Antigen Concentration and Genotype in Relation to Myocardial Infarction in the North and South of Europe." Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 22, no. 5, 2002, pp. 867-73.
Juhan-Vague I, Morange PE, Aubert H, et al. Plasma thrombin-activatable fibrinolysis inhibitor antigen concentration and genotype in relation to myocardial infarction in the north and south of Europe. Arterioscler Thromb Vasc Biol. 2002;22(5):867-73.
Juhan-Vague, I., Morange, P. E., Aubert, H., Henry, M., Aillaud, M. F., Alessi, M. C., ... Humphries, S. E. (2002). Plasma thrombin-activatable fibrinolysis inhibitor antigen concentration and genotype in relation to myocardial infarction in the north and south of Europe. Arteriosclerosis, Thrombosis, and Vascular Biology, 22(5), pp. 867-73.
Juhan-Vague I, et al. Plasma Thrombin-activatable Fibrinolysis Inhibitor Antigen Concentration and Genotype in Relation to Myocardial Infarction in the North and South of Europe. Arterioscler Thromb Vasc Biol. 2002 May 1;22(5):867-73. PubMed PMID: 12006404.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Plasma thrombin-activatable fibrinolysis inhibitor antigen concentration and genotype in relation to myocardial infarction in the north and south of Europe. AU - Juhan-Vague,I, AU - Morange,P E, AU - Aubert,H, AU - Henry,M, AU - Aillaud,M F, AU - Alessi,M C, AU - Samnegård,A, AU - Hawe,E, AU - Yudkin,J, AU - Margaglione,M, AU - Di Minno,G, AU - Hamsten,A, AU - Humphries,S E, AU - ,, PY - 2002/5/15/pubmed PY - 2002/6/20/medline PY - 2002/5/15/entrez SP - 867 EP - 73 JF - Arteriosclerosis, thrombosis, and vascular biology JO - Arterioscler. Thromb. Vasc. Biol. VL - 22 IS - 5 N2 - The thrombin-activatable fibrinolysis inhibitor (TAFI) is a recently described inhibitor of fibrinolysis that decreases plasminogen binding to the fibrin surface. The plasma TAFI concentration is almost entirely genetically determined. We investigated whether plasma TAFI levels and polymorphisms located in the TAFI gene could constitute risk markers of myocardial infarction (MI). Plasma TAFI antigen (Ag) levels were assayed by ELISA and 2 TAFI gene polymorphisms (Ala147Thr and C+1542G in the 3' untranslated region) were determined in a large European case-control study. This study compared 598 men recruited 3 to 6 months after MI with 653 age-matched controls from North Europe (Stockholm, Sweden, and London, England) and South Europe (Marseilles, France, and San Giovanni Rotondo, Italy). A TAFI Ag value above the 90th percentile was associated with a significantly lower risk of MI (odds ratio 0.55, P<0.02), indicating that elevated TAFI may be protective against MI. As previously shown, the 2 TAFI gene polymorphisms were in strong linkage disequilibrium and were associated with the TAFI Ag concentration, with carriers of the Thr147 and 1542C alleles having higher levels (P<0.0005). These effects were similar in controls and cases and in each center. There was a difference in allele frequency between cases and controls for the Ala147Thr polymorphism, with Thr147 allele carriers being more frequent in controls than in cases in 2 centers, Stockholm (P=0.03) and San Giovanni Rotondo (P=0.03); the odds ratio for the entire cohort was 0.78 (P<0.05). In conclusion, patients with a recent MI presented lower values of TAFI Ag and higher frequencies of the "TAFI-decreasing" alleles. The geographical differences observed do not contribute to explaining the North-South gradient in MI risk in Europe. SN - 1524-4636 UR - https://www.unboundmedicine.com/medline/citation/12006404/Plasma_thrombin_activatable_fibrinolysis_inhibitor_antigen_concentration_and_genotype_in_relation_to_myocardial_infarction_in_the_north_and_south_of_Europe_ L2 - http://www.ahajournals.org/doi/full/10.1161/01.atv.0000015445.22243.f4?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -