New Coagulation Factor V Gene Polymorphisms Define a Single and Infrequent Haplotype Underlying the Factor V Leiden Mutation in Mediterranean Populations and Indians

E Castoldi; B Lunghi; F Mingozzi; P Loannou; G Marchetti; F Bernardi

doi:10.1055/s-0038-1657683

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1997; 78(03): 1037-1041
DOI: 10.1055/s-0038-1657683

Rapid Communication

Schattauer GmbH Stuttgart

New Coagulation Factor V Gene Polymorphisms Define a Single and Infrequent Haplotype Underlying the Factor V Leiden Mutation in Mediterranean Populations and Indians

E Castoldi

¹Dipartimento di Biochimica e Biologia Molecolare, Universitá di Ferrara, Italy

,

B Lunghi

¹Dipartimento di Biochimica e Biologia Molecolare, Universitá di Ferrara, Italy

,

F Mingozzi

¹Dipartimento di Biochimica e Biologia Molecolare, Universitá di Ferrara, Italy

,

P Loannou

²Dept. of Molecular Genetics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus

,

G Marchetti

¹Dipartimento di Biochimica e Biologia Molecolare, Universitá di Ferrara, Italy

,

F Bernardi

¹Dipartimento di Biochimica e Biologia Molecolare, Universitá di Ferrara, Italy

› Institutsangaben

Abstract

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Summary

Two novel polymorphisms were identified in the factor V gene by direct sequencing of intronic areas. One of them, located in intron 9, is the marker closest to the Leiden mutation ever described, whereas the other, in intron 16, displays a rare allele invariantly associated to the mutation. Allele-specific amplification protocols were designed to perform extensive screenings for both polymorphic sites. The new markers were used in combination with six previously described polymorphisms to define specific factor V gene haplotypes. Haplotype investigations in 506Q homozygous thrombotic patients and normal controls showed the presence of a single haplotype underlying the factor V Leiden mutation in Mediterranean populations (among which Greek Cypriots, where the R506Q mutation is particularly frequent) and Indians. When traced in the absence of the Leiden mutation, the background haplotype was found to be present and roughly as frequent as the mutation itself in these populations. These findings indicate a single mutational event, that probably occurred outside Europe, as the cause of the Leiden mutation and provide a powerful tool to investigate its evolutionary history.

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Referenzen

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