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Detection of new polymorphic markers in the factor V gene: association with factor V levels in plasma
B Lunghi1, L Iacoviello, D Gemmati
1Dip. di Biochimica e Biologia Molecolare, Università di Ferrara, Italy.
Insights
Researchers identified novel factor V gene polymorphisms, including the R2 allele, linked to lower factor V plasma activity. This suggests a genetic component in factor V levels and deficiency, with R2 acting as a marker for an unknown defect.
Area of Science:
- Genetics
- Hematology
- Molecular Biology
Background:
- Factor V is crucial for blood coagulation.
- Partial factor V deficiency can occur, but its genetic basis is not fully understood.
- Genetic variations in the factor V gene may influence plasma factor V levels.
Purpose of the Study:
- To investigate novel polymorphisms in the factor V gene.
- To determine the association between these polymorphisms and factor V plasma activity.
- To explore the genetic basis of factor V deficiency.
Main Methods:
- Analysis of factor V gene exon 13 for novel polymorphisms.
- Genotyping of subjects including those with partial factor V deficiency.
- Correlation analysis between R2 allele frequency and plasma factor V activity.
- Family studies to assess co-inheritance patterns.
Main Results:
- Three novel polymorphisms identified: Ser1240, His1299Arg, and Leu1257Ile.
- The Arg1299 (R2 allele) showed an inverse correlation with mean plasma factor V activity.
- Family studies confirmed co-inheritance of low factor V activity and the R2 allele.
- Reduced factor V activity associated with R2 was asymptomatic and lacked detectable abnormal molecules.
Conclusions:
- The R2 allele is likely a marker linked to an unknown genetic defect causing reduced factor V levels, not a functional polymorphism itself.
- This study provides the first evidence for a genetic component influencing plasma factor V levels.
- Genetic linkage between the factor V gene and factor V deficiency is established, with defined haplotypes valuable for studying factor V defects.
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.