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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:755-759.)
© 1997 American Heart Association, Inc.

Articles

Gene Polymorphisms Predicting High Plasma Levels of Coagulation and Fibrinolysis Proteins

A Study in Centenarians

P.M. Mannucci; D. Mari; G. Merati; F. Peyvandi; L. Tagliabue; E. Sacchi; E. Taioli; P. Sansoni; S. Bertolini; ; C. Franceschi

From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Epidemiology Unit, IRCCS Maggiore Hospital and Geriatric Unit, Institute of Internal Medicine, University of Milano (P.M.M., D.M., G.M., F.P., L.T., E.S., E.T.); the Institute of Clinical Medicine, University of Parma (P.S.); the Department of Internal Medicine, University of Genoa (S.B.); and the Department of Biochemical Sciences, University of Modena (C.F.), Italy.

Correspondence to Dr P.M. Mannucci, via Pace 9, 20122 Milano, Italy. E-mail pmm_isth{at}energy.it

Abstract Gene polymorphisms associated with the plasma levels of fibrinogen, factor VII, and plasminogen activator inhibitor 1 (PAI-1)—hemostasis proteins that help to predict the risk of atherothrombotic disease—were compared in 124 healthy individuals 100 years old and 130 young, healthy individuals to identify genetic influences on extreme longevity. We investigated the restriction fragment length polymorphism G/A^-455 located in the promoter of the ß-fibrinogen gene, the guanine insertion/deletion polymorphism 4G/5G in the promoter of the PAI-1 gene, and the R353Q substitution polymorphism in exon 8 of the factor VII gene. Alleles and genotypes associated with elevated plasma levels of fibrinogen and factor VII were found with similar frequencies in centenarians and in the comparison group. However, in centenarians there was a significantly higher frequency of the 4G allele and of the homozygous 4G4G genotype associated with high PAI-1 levels. Since high PAI-1 is considered a predictor of recurrent myocardial infarction in young men, it is intriguing that the corresponding genetic marker is more frequent in centenarians who have escaped major age-related atherothrombotic disease and reached the extreme limits of human life. Homozygosity for the 4G allele, despite its association with impaired fibrinolysis, is compatible with successful aging.

Key Words: centenarians • fibrinogen • factor VII • plasminogen activator inhibitor 1 • gene polymorphisms

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