Detection of new polymorphic markers in the factor V gene: association with factor V levels in plasma.

Abstract

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 (Ser1240) and two causing aminoacid substitutions (His1299Arg, Leu1257Ile). An increasing frequency of the Arg1299 (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 tools for the study of factor V defects.

• Authors: B Lunghi, L Iacoviello, D Gemmati, M G Dilasio, E Castoldi, M Pinotti, G Castaman, R Redaelli, G Mariani, G Marchetti, F Bernardi
• Journal: Thrombosis and haemostasis (Thromb Haemost) Vol. 75 Issue 1 Pg. 45-8 (Jan 1996) ISSN: 0340-6245 [Print] Germany
• PMID: 8713778 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Genetic Markers
• Factor V

Topics

• Base Sequence
• Case-Control Studies
• Factor V (genetics, metabolism)
• Female
• Genetic Markers
• Haplotypes
• Heterozygote
• Homozygote
• Humans
• Male
• Molecular Sequence Data
• Polymorphism, Genetic
• Repetitive Sequences, Nucleic Acid
• Thrombosis (genetics)