Prevalence of rare F5 variants in general population from Bosnia and Herzegovina

Adna Ašić,Wolfgang Höppner,Ramona Salazar,Niels Storm,Damir Marjanović,Dragan Primorac,Serkan Doğan

doi:10.1007/s11033-021-06519-2

Abstract

Human gene F5, encoding coagulation factor V, was previously reported to be highly polymorphic. Apart from FV Leiden, several other rare variants have been detected in clinical practice and associated with thrombotic events, especially in cases when patient's phenotype and FV Leiden genotype were not in agreement. In this study, the prevalence of 17 rare F5 variants has been studied on a sample of 130 healthy adult individuals from the general Bosnian-Herzegovinian population. DNA was isolated from buccal swab samples, while genotyping was performed using MALDI-TOF MS method. The results have shown that Asp2194Gly and Met2120Thr are polymorphic in the study population with minor allele frequencies of 0.077 and 0.073, respectively. Additionally, these two variants were mutually exclusive with FV Leiden and none of them was positively associated with participants' family history of cardiovascular or cerebrovascular diseases. While the obtained results are in agreement with previously reported data for the general Caucasian populations, it is worth noting that only two rare F5 variants were detected in the study population, albeit at considerable frequencies. Still, scientific information on rare F5 variants is rather scarce and further studies aiming to assess functional importance of these variants, as well as their role as prothrombotic factors are necessary.

Highlights

Coagulation factor V (FV) is encoded by F5 gene whose mRNA product is 6.8 kb long and has 25 exons, while the corresponding polypeptide is 2,224 amino acids long
The results have shown that Asp2194Gly and Met2120Thr are polymorphic in the study population with minor allele frequencies of 0.077 and 0.073, respectively. These two variants were found to be mutually exclusive with FV Leiden and none of them was positively associated with participants’ family history of cardiovascular or cerebrovascular diseases
While the obtained results are in agreement with previously reported data for the general Caucasian populations, it is worth noting that only two rare F5 variants were detected in the study population, albeit at considerable frequencies

Summary

Introduction

Coagulation factor V (FV) is encoded by F5 gene whose mRNA product is 6.8 kb long and has 25 exons, while the corresponding polypeptide is 2,224 amino acids long. The most probable one relates the frequency of F5 DNA variants with its dual role as procoagulant and anticoagulant protein, whereby this gene is usually described as Dr Jekyll and Mr Hyde of human coagulation [7]. According to the previously published literature [8], rare F5 variants have been detected in clinical practice when the results of FVL genotyping and observed patient’s phenotype were not in alignment, implying other underlying mutations. Human gene F5, encoding coagulation factor V, was previously reported to be highly polymorphic. Apart from FV Leiden, an array of other rare variants has been detected in clinical practice and associated with thrombotic events, especially in cases when patient’s phenotype and FV Leiden genotype were not in agreement

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