FREQUENCY AND ASSOCIATION OF 1691 (G>A) FVL,
20210 (G>A) PT AND 677 (C>T) MTHFR WITH
DEEP VEIN THROMBOSIS IN THE POPULATION
OF BOSNIA AND HERZEGOVINA Jusić-Karić A, Terzić R, Jerkić Z, Avdić A, Pođanin M *Corresponding Author: Amela Jusić-Karić, Ph.D., Faculty of Science and Mathematics, University of Tuzla,
Univerzitetska 4, 75 000 Tuzla, Bosnia and Herzegovina. Tel: +387-61-289-217. Fax: +387-35-320-861.
E-mail: amela.jusic @untz.ba page: 43
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INTRODUCTION
Deep vein thrombosis (DVT) is the most common
clinical manifestation of venous thromboembolism
with multi factorial pathogenesis. Venous thromboembolism
(VTE) occurs as a result of interaction
of series of different risk factors including acquired
and hereditary conditions. Generally, a tendency toward
venous thrombosis can arise from hyperactive
anticoagulant pathways, hypoactive anticoagulant
mechanisms or hypoactive fibrinolysis [1]. Venous
thromboembolism is highly heritable and multiple coinherited
genetics risk factors increase the incidence
risk [2]. The most common identified mutations interfering
with VTE are: 1691 (G>A) factor V Leiden
(FVL), 20210 (G>A) prothrombin (PT), deficiency
of protein C, protein S and antithrombin III.
Blood coagulation factor V is coded by a gene
located on the long arm of chromosome 1 (1q23) and
consists of 25 exons and 24 introns [3]. Transition in
exon 10 of gene F5 causes a substitution (R506Q)
known as factor V Leiden that has been recognized as
the most prevalent genetic risk factor for VTE. Heterozygotes
and homozygotes of the 1691 mutation are associated with a 7- and 80-fold increased risk of venous
thrombosis, respectively [4]. It has been estimated that
the prevalence of 1691 mutation in the patients with
DVT varies between 20.0 and 30.0% [5]. Estimated
frequencies of 1691 mutation among Caucasians range
from 2.0 to 9.5%, moderate prevalence is observed in
Hispanic Americans and Indians (1.0-5.0%), whereas
it is rare in Asians and Africans (<1.0%) [6,7].
A G to A transition at position 20210 within the
3’ untranslated region (3’UTR) of the prothrombin
gene has been identified as a risk factor for thrombosis
[8]. This substitution in the PT gene results in
an increased gene expression that could lead into
increasing activity of prothrombin in plasma. Geographic
difference in the frequency of the 20210 mutation
exists in healthy individuals, with the highest
frequencies observed in Europe and the Middle East
[9], whereas its prevalence among Asians and Africans
is <1.0% [4]. According to the literature, the
relative risk of thrombosis is twice times higher in patients
with the 20210 mutation, three times higher in
patients with the 1691 mutation and six times higher
in patients who have of both mutations.
The C to T transition at position 677 in exon 4 of
the methylene tetrahydrofolate reductase (MTHFR)
gene is recognized as a mutation that interferes with
cysteine metabolism and leads to increased levels
of plasma homo-cysteine in homozygotes carrying
the 677 mutation. The 677 mutation is common in
the general population and has been recognized as
the risk factor for cardiovascular diseases [10]. The
prevalence of 677 ranges 30.0 to 50.0% (heterozygotes)
and 9.0 to 12.0% (homozygotes) in the general
population. The exact impact of the 677 mutation on
the occurrence of venous thrombosis has been unclear
so far, but it is obvious that the presence of hyperhomocysteinemia
increases the risk for thrombosis [11].
Although 1691, 20210 and 677 mutations have
been recognized as the most common risk factor for
VTE, there are only a few reports of prevalence of
these mutations in the healthy Bosnian population
[12,13]. Our study was conducted in order to investigate
the frequency of these mutations and their association
with DVT in the Bosnian population.
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