Prevalence of thrombophilic mutations of FV Leiden, prothrombin G20210A and PAI-1 4G/5G and their combinations in a group of 1,450 healthy middle-aged individuals in the Prague and Central Bohemian regions (results of FRET real-time PCR assay)

Summary

Background.
Factor V Leiden (G1691A) and prothrombin gene (FII G20210A) mutations are independent risk factors of venous thrombosis and this risk is further increased by the combined genotype 4G/4G PAI-1.

Aim.
The primary objective was to identify the frequency of mutations of minor alleles and genotypes of FVL, FII G20210A and PAI-1 4G/5G in healthy Caucasians in the Prague and Central Bohemia regions. The secondary objective was to identify the occurrence of their mutual combinations.

Method.
Genotyping was performed in 1,450 healthy individuals (blood donors, 981 men and 469 women) using robotic DNA isolation and subsequent PCR and melting curve analysis (Light Cycler 480 System, Roche).

Results.
The minor allele frequencies in FV Leiden and FII G20210A mutations were 4.5 % and 1.3% respectively. The frequency of the 4G PAI-1 allele was 55.9%. The genotype frequencies were as follows: GG 91.10%, GA 8.83% and AA 0.07% for FV Leiden; GG 97.38%, GA 2.55% and AA 0.07% for FII G20210A and 4G/4G 30.69%, 4G/5G 50.34% and 5G/5G 18.97% for PAI-1. No differences in these frequencies were found between the genders. The occurrence of the combined heterozygous FII and heterozygous FV Leiden mutations was 0.14%. The PAI-1 4G/4G genotype was combined with the heterozygous FV Leiden mutation in 2.83% of cases and with the heterozygous FII mutation in 0.62% of cases.

Conclusions.
The found frequencies of genotypes and alleles confirm a relatively high prevalence of hereditary thrombophilia in the Czech Republic.

Key words:
FV Leiden, FII G20210A, PAI-1 4G/5G, genotype, alleles, prevalence.