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
|
|
DISCUSSION
The observed prevalence of the 1691mutation
in this study corresponds to the reported prevalence
in the healthy Caucasian population [2,17-20]. The
relationship between the 1691 mutation and VTE is
commonly recognized [21]. According to the data,
about 18.0% of patients with first occurrence of DVT
and about 40.0% of thrombophilic families carry
1691 [5,14]. In this study, the 1691 mutation was
shown to be significantly associated with DVT with
an OR (95%CI) = 6.0 (2.62-14.14); p = 0.0001. The
current observations are consistent with other reports
from other countries in the region [22-24].
The second genetic risk factor for vein thrombosis,
the 20210 mutation, was present in the Caucasian
population with a frequency of 0.7 to 4.0%, with an
average close to 2.0%. The prevalence of this mutation
was higher in the Southern European countries than
in Northern countries, in spite of presence of overlapping
between north and south. The 20210 mutation
was found to be very rare or even absent in Asian
and African populations and American Indians and
Australian Aborigines [25]. The greatest frequency of
20210 is reported in Hispanics and Mexican Mestizos.
The prevalence of this mutation in patients with VTE
was 8.0% and an even higher prevalence (18.0%)
was found in selected families with thrombosis. In
our investigated group, three out of 111 patients were
heterozygotes for the 20210 mutation. In the control
group, the 20210 mutation was absent. Our results
are in contrast with the results of Adler et al. [13],
who observed a frequency of the 20210 mutation in
6.0% out of 100 healthy individuals from Bosnia and
Herzegovina. Discrepancy in results from our study
and the study of Adler et al. [13], could be explained
by the small number of subjects in the subgroups and
inadequate female-to-male ratio in the latter study.
This ratio is not sufficient for generalization of the
data on the whole Bosnian population, due to the small
sample size and limited power of the study. Absence
of the 20210 mutation in our control group can also
partly explain its lower frequency in the patients.
Two common polymorphisms of the MTHFR
gene, 677 and 1298 (A>C), appear to be related to
early coronary disease but their relationship with VTE
is conflicting [26,27]. Many studies have shown that
individuals who have both polymorphic alleles have moderately increased concentration of homocysteine.
In reference [28] is reported that hyperhomocysteinemia
is a weak risk factor for VTE. The prevalence of
the T allele varies among races and ethnic groups. In
our study, allele and genotype frequencies of the 677
mutation did not differ significantly between healthy
subjects and patients with DVT. These results are
consistent with the data of Alfirevic et al. [2], Adler
et al. [13], Tsai et al. [29] and Beyan and Beyan [30].
Researching the distribution of the 1691, 20210
and 677 mutations according to gender is especially
important in women because they undergo hemostatic
changes during the pregnancy. We did not observe
the difference in the frequencies of these mutations
between men and women in the patients’ group or in
the control group. However, we found statistically
significant difference in distribution of the 1691 mutation
between women with DVT and women in the
control group and between men in compared groups.
We can only speculate that men and women who were
heterozygotes or homozygotes for the 1691 mutation
were more prone to develop DVT. Literature data have
shown that the combined effect of more than one genetic
variant can double or triple the risk for VTE. The
combination of the most frequent genetics risk factor,
1691 and 20210, has been frequently found in patients
with VTE. The prevalence of 0.4% of both mutations
in individuals with VTE was observed by Ridker et
al. [6]. The high frequency of 1691 and 20210 (3.0%)
was demonstrated in Croatian patients with DVT [22].
Similar results about coexisting heterozygous forms
of 1691 and 20210 were reported by Ehrenforth et al.
[31] (11.0%), Zoller et al. [32] (10.0%) and Ferraresi
et al. [33] (14.0%). Observed frequency of those two
mutations in our study was 1.16% in the patients’
group. The presence of both the 1691 and 20210 mutations
increased the risk of recurrent DVT by a factor
of 2.6 and the risk of a spontaneous recurrence by a
factor of 3.7, as compared with the risk in patients
who were heterozygous for the 1691 mutation alone
[34]. In contrast to the study by De Stefano et al. [34],
we did not confirm a relationship between compound
heterozygosity of 1691 and 20210 with DVT ,which
might be due to a relatively small size of our study
population. Our study results indicated that the 1691
and 677 mutations tend to coexist in a heterozygous
form in 14.90% of patients. In large meta-analysis
study [35], it was demonstrated that there was no interaction
of the 677 variant with 1691 and with 20210
in risk of developing VTE, confirming the hypothesis
that 677 is not a risk factor for VTE.
|
|
|
|
 |
Number 27
VOL. 27 (2), 2024 |
Number 27
VOL. 27 (1), 2024 |
Number 26
Number 26 VOL. 26(2), 2023 All in one |
Number 26
VOL. 26(2), 2023 |
Number 26
VOL. 26, 2023 Supplement |
Number 26
VOL. 26(1), 2023 |
Number 25
VOL. 25(2), 2022 |
Number 25
VOL. 25 (1), 2022 |
Number 24
VOL. 24(2), 2021 |
Number 24
VOL. 24(1), 2021 |
Number 23
VOL. 23(2), 2020 |
Number 22
VOL. 22(2), 2019 |
Number 22
VOL. 22(1), 2019 |
Number 22
VOL. 22, 2019 Supplement |
Number 21
VOL. 21(2), 2018 |
Number 21
VOL. 21 (1), 2018 |
Number 21
VOL. 21, 2018 Supplement |
Number 20
VOL. 20 (2), 2017 |
Number 20
VOL. 20 (1), 2017 |
Number 19
VOL. 19 (2), 2016 |
Number 19
VOL. 19 (1), 2016 |
Number 18
VOL. 18 (2), 2015 |
Number 18
VOL. 18 (1), 2015 |
Number 17
VOL. 17 (2), 2014 |
Number 17
VOL. 17 (1), 2014 |
Number 16
VOL. 16 (2), 2013 |
Number 16
VOL. 16 (1), 2013 |
Number 15
VOL. 15 (2), 2012 |
Number 15
VOL. 15, 2012 Supplement |
Number 15
Vol. 15 (1), 2012 |
Number 14
14 - Vol. 14 (2), 2011 |
Number 14
The 9th Balkan Congress of Medical Genetics |
Number 14
14 - Vol. 14 (1), 2011 |
Number 13
Vol. 13 (2), 2010 |
Number 13
Vol.13 (1), 2010 |
Number 12
Vol.12 (2), 2009 |
Number 12
Vol.12 (1), 2009 |
Number 11
Vol.11 (2),2008 |
Number 11
Vol.11 (1),2008 |
Number 10
Vol.10 (2), 2007 |
Number 10
10 (1),2007 |
Number 9
1&2, 2006 |
Number 9
3&4, 2006 |
Number 8
1&2, 2005 |
Number 8
3&4, 2004 |
Number 7
1&2, 2004 |
Number 6
3&4, 2003 |
Number 6
1&2, 2003 |
Number 5
3&4, 2002 |
Number 5
1&2, 2002 |
Number 4
Vol.3 (4), 2000 |
Number 4
Vol.2 (4), 1999 |
Number 4
Vol.1 (4), 1998 |
Number 4
3&4, 2001 |
Number 4
1&2, 2001 |
Number 3
Vol.3 (3), 2000 |
Number 3
Vol.2 (3), 1999 |
Number 3
Vol.1 (3), 1998 |
Number 2
Vol.3(2), 2000 |
Number 2
Vol.1 (2), 1998 |
Number 2
Vol.2 (2), 1999 |
Number 1
Vol.3 (1), 2000 |
Number 1
Vol.2 (1), 1999 |
Number 1
Vol.1 (1), 1998 |
|
|
