Activated protein C resistance caused by a common factor V mutation has a single origin

Area of Science:

• Genetics
• Hematology
• Human Evolution

Background:

• A specific mutation (FV:R506Q) in the factor V gene causes activated protein C resistance.
• This mutation is linked to a lifelong increased risk of venous thrombosis.
• The FV:R506Q mutation is prevalent in Caucasians but rare in other populations.

Purpose of the Study:

• To determine allele frequencies of the FV:R506Q mutation and associated dimorphisms in Swedish populations.
• To investigate linkage disequilibrium between FV:R506Q and nearby genetic markers.
• To explore the ancestral origins of the FV:R506Q mutation in Sweden.

Main Methods:

• Genotyping of 140 healthy Swedish volunteers and 110 homozygotes for the FV:R506Q mutation.
• Analysis of allele frequencies for FV:R506Q and four other nucleotide dimorphisms (C/T at 2298, 2325; A/G at 2379, 2391).
• Assessment of linkage disequilibrium patterns.

Main Results:

• Significant linkage disequilibrium was observed between the FV:R506Q mutation and the four studied dimorphisms.
• A single FV:R506Q haplotype was identified in all homozygous individuals.
• This suggests a shared ancestral origin for Swedish individuals carrying the FV:R506Q mutation.

Conclusions:

• The FV:R506Q mutation and specific linked dimorphisms in Swedish populations indicate a common ancestral haplotype.
• This finding provides strong evidence for a common ancestor among Swedish individuals with the FV:R506Q mutation.
• Further research into population genetics can elucidate the evolutionary history of thrombotic risk factors.