Detection of New Polymorphic Markers in the Factor V Gene: Association with Factor V Levels in Plasma

B Lunghi; L Iacoviello; D Gemmati; M G Dilasio; E Castoldi; M Pinotti; G Castaman; R Redaelli; G Mariani; G Marchetti; F Bernardi

doi:10.1055/s-0038-1650219

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1996; 75(01): 045-048
DOI: 10.1055/s-0038-1650219

Original Article

Schattauer GmbH Stuttgart

Detection of New Polymorphic Markers in the Factor V Gene: Association with Factor V Levels in Plasma

Authors

B Lunghi

¹The Dip. di Biochimica e Biologia Molecolare, Consorzio Mario Negri Sud, S. Maria Imbaro, Italy
L Iacoviello

²The “Angela Valenti” Lab. Thrombosis Pharmacology, 1st. di Ricerche Farmacologiche Mario Negri; Consorzio Mario Negri Sud, S. Maria Imbaro, Italy
D Gemmati

³The Centro Emostasi e Trombosi, Università di Ferrara, Consorzio Mario Negri Sud, S. Maria Imbaro, Italy
M G Dilasio

¹The Dip. di Biochimica e Biologia Molecolare, Consorzio Mario Negri Sud, S. Maria Imbaro, Italy
E Castoldi

¹The Dip. di Biochimica e Biologia Molecolare, Consorzio Mario Negri Sud, S. Maria Imbaro, Italy
M Pinotti

¹The Dip. di Biochimica e Biologia Molecolare, Consorzio Mario Negri Sud, S. Maria Imbaro, Italy
G Castaman

⁴The Divisione di Ematologia - CRS Malattie Emorragiche e Trombotiche, Osp. S. Bortolo, Vicenza, Italy
R Redaelli

⁵The Div. di Ematologia, Osp. Niguarda, Milano, Italy
G Mariani

⁶The Dip. di Biopatologia Umana, Sezione di Ematologia, Università La Sapienza, Roma; Italy
G Marchetti

¹The Dip. di Biochimica e Biologia Molecolare, Consorzio Mario Negri Sud, S. Maria Imbaro, Italy
F Bernardi

¹The Dip. di Biochimica e Biologia Molecolare, Consorzio Mario Negri Sud, S. Maria Imbaro, Italy

Abstract

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Summary

Three novel polymorphisms were found in the repeated region of the large exon 13 of factor V gene, one giving rise to a codon dimorphism (Serl240) and two causing aminoacid substitutions (Hisl299Arg, Leul257Ile). An increasing frequency of the Argl299 (R2 allele) correlated with a decreasing mean plasma factor V activity in the groups of subjects under study, which included 26 unrelated subjects with partial factor V deficiency. Family studies supported the co-inheritance both of low factor V activity and of R2 allele. The reduction of factor V activity associated with the R2 allele was not clinically symptomatic even in the homozygous condition and was characterized by a parallel reduction of antigen in plasma, in which abnormal molecules were not detected. Data suggest that the R2 allele represents a marker in linkage with an unknown defect rather than a functional polymorphism.

These studies provide the first evidence of a genetic component in determining factor V levels in plasma and of a genetic linkage between the factor V gene and factor V deficiency. They also define specific haplotypes which are associated with factor V deficiency or with APC resistance (Arg506Gln) and are valuable fools for the study of factor V defects.

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References

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