title: 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.affiliation: Dip. di Biochimica e Biologia Molecolare, Università di Ferrara, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Lunghi
authors.forename: L
authors.initials: L
authors.lastname: Iacoviello
authors.forename: D
authors.initials: D
authors.lastname: Gemmati
authors.forename: M G
authors.initials: MG
authors.lastname: Dilasio
authors.forename: E
authors.initials: E
authors.lastname: Castoldi
authors.forename: M
authors.initials: M
authors.lastname: Pinotti
authors.forename: G
authors.initials: G
authors.lastname: Castaman
authors.forename: R
authors.initials: R
authors.lastname: Redaelli
authors.forename: G
authors.initials: G
authors.lastname: Mariani
authors.forename: G
authors.initials: G
authors.lastname: Marchetti
authors.forename: F
authors.initials: F
authors.lastname: Bernardi
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D005165:Factor V / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005819:Genetic Markers; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D013927:Thrombosis / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D005165:Factor V