DETECTION OF NEW POLYMORPHIC MARKERS IN THE FACTOR-V GENE - ASSOCIATION WITH FACTOR-V LEVELS IN PLASMA

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.