B. Lunghi et al., DETECTION OF NEW POLYMORPHIC MARKERS IN THE FACTOR-V GENE - ASSOCIATION WITH FACTOR-V LEVELS IN PLASMA, Thrombosis and haemostasis, 75(1), 1996, pp. 45-48
Three novel polymorphisms were found in the repeated region of the lar
ge exon 13 of factor V gene, one giving rise to a codon dimorphism (Se
r1240) and two causing aminoacid substitutions (His1299Arg, Leu1257Ile
). An increasing frequency of the Arg1299 (R2 allele) cor related 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 p
rovide 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 a
re associated with factor V deficiency or with APC resistance (Arg506G
ln) and are valuable tools for the study of factor V defects.